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A 3ª edição do Congresso Internacional de Estudantes e Profissionais da Saúde – DELTA SAÚDE, realizou-se de forma presencial no período de 04 a 06 de novembro de 2022, no Centro de Convenções do Hotel SESC Praia, Luis Correia, Piauí. O Delta Saúde 2022 trouxe como tema geral: “O pós-pandemia e os principais desafios da saúde global”; e as discussões foram norteadas pelos eixos centrais, a saber: a) Pandemia de COVID-19, b) Vigilância em Saúde, c) Saúde Pública e a Atenção Primária, d) Saúde Mental, e) Doenças Crônicas e Doenças Transmissíveis, f) Educação, Formação e Trabalho na Saúde, g) Inovação em Saúde, h) Eixos Transversais. O evento foi criado em 2017 e nesta edição alcançamos pelo menos 10 estados brasileiros em participação direta, palestrantes, convidados, além dos conferencistas internacionais on-line. Esta diversidade aliada a qualidade dos trabalhos apresentados, contribuiu de forma decisiva para o alcance dos objetivos do congresso que primam pela qualificação do ensino na saúde de acadêmicos e pós-graduandos, pelo fortalecimento das práticas profissionais nos serviços de saúde, e pelo incentivo à produção científica. A programação do evento foi composta por palestras nacionais e internacionais, mesas multidisciplinares, cursos livres, seminários, rodas de conversas, encontros e sessões de trabalhos com apresentações nas modalidades: Comunicações Orais e Pôsteres; e com publicação das pesquisas científicas nos Anais do congresso. O evento conto u com 692 inscritos, e destes 42 foram palestrantes que abrilhantaram a programação do congresso. Recebemos 746 resumos para avaliação, e foram apresentados presencialmente 536 trabalhos, sendo 42 premiados com menção honrosa. O evento foi idealizado pela Sociedade Delta Científica e SBCSaúde, teve o apoio do SESC-PI e da Doity, além do apoio científico da FIOCRUZ Piauí, da Editora Pasteur, dos núcleos de pesquisa NUPCelt/UFPI, NAPsiTO/UFPI/UFDPar e NPPM/UFPI; e dos programas de residência multiprofissional RMSFC/UESPI e PRMSF/UFPI/UFDPar. O evento também contou com a parceria de empresas patrocinadoras e expositoras, que tiveram da Comissão Organizadora reciprocidade em suas demandas, a saber: Instituto UniEducacional, WM Saúde e The Nutri Store/PACCO.

Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais, Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior, Bio-Manguinhos/FIOCRUZ, PROEP/ CPqRR/FIOCRUZ, Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico?CNPq (grant nos. 444417/2014-1 and 458134/2014-7), and Programa Nacional de Imuniza??es, Secretaria de Vigil?ncia em Sa?de?Minist?rio da Sa?de, Brazil (grant no. TC 277/2013). O.A.M.-F., A.T.-C., and L.R.A. received research fellowships from CNPq. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Secretaria Municipal de Sa?de. Belo Horizonte, MG, Brasil. Secretaria do Estado de Sa?de de Minas Gerais. Belo Horizonte, MG, Brasil. Funda??o Oswaldo Cruz. Escola Nacional de Sa?de P?blica. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil. Funda??o Oswaldo Cruz. Instituto de Tecnologia em Imunobiol?gicos Bio-Manguinhos. Rio de Janeiro, RJ, Brasil. Universidade Federal de Alfenas. Alfenas, MG, Brazil. Universidade de Bras?lia. Bras?lia, DF, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Bras?lia, DF, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Bras?lia, DF, Brasil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Instituto Ren? Rachou. Belo Horizonte, MG, Brazil. We evaluated the duration of neutralizing antibodies and the status of 17DD vaccine?specific T- and B-cell memory following primary and revaccination regimens for yellow fever (YF) in Brazil. We observed progressive decline of plaque-reduction neutralization test (PRNT) seropositivity and of the levels of effector memory CD4+ and CD8+ T cells, as well as interferon-?+CD8+ T cells, 10 years after primary vaccination. Revaccination restored PRNT seropositivity as well as the levels of effector memory CD4+, CD8+, and interferon-?+CD8+ T cells. Moreover, secondary or multiple vaccinations guarantee long-term persistence of PRNT positivity and cell-mediated memory 10 years after booster vaccination. These findings support the relevance of booster doses to heighten the 17DD-YF?specific immune response to guarantee the long-term persistence of memory components. Secondary or multiple vaccinations improved the correlates of protection triggered by 17DD-YF primary vaccination, indicating that booster regimens are needed to achieve efficient immunity in areas with high risk for virus transmission.

One patient presented hyporexia, asthenia, adynamia, and jaundice two months after acute yellow fever (YF) onset; plus laboratory tests indicating hepatic cytolysis and a rebound of alanine and aspartate transaminases, and total and direct bilirubin levels. Laboratory tests discarded autoimmune hepatitis, inflammatory or metabolic liver disease, and new infections caused by hepatotropic agents. Anti-YFV IgM, IgG and neutralizing antibodies were detected in different times, but no viremia. A liver biopsy was collected three months after YF onset and tested positive for YFV antigens and wild-type YFV-RNA (364 RNA-copies/gram/liver). Transaminases and bilirubin levels remained elevated for five months, and the arresting of symptoms persisted for six months after the acute YF onset. Several serum chemokines, cytokines, and growth factors were measured. A similar immune response profile was observed in the earlier phases of the disease, followed by more pronounced changes in the later stages, when transaminases levels returned to normal. The results indicated viral persistence in the liver and continual liver cell damage three months after YF onset and reinforced the need for extended follow-ups of YF patients. Further studies to investigate the role of possible viral persistence and the immune response causing relapsing hepatitis following YF are also necessary.

Eosinophils are multifunctional cells that have cytotoxic proinflammatory activities and stimulate CD4+ T-cells in experimental models of allergy and parasitic infections. Eosinophils, when exposed to antigens, are activated, expressing the CD38/CD69 molecules and exhibited increased expression of major histocompatibility complex (MHC-II), CD80 and CD86, suggesting they play a role upon Toxocara canis antigen stimulation. In the present study, we evaluated the profile of eosinophils using conventional and image flow cytometry upon experimental T. canis infection. T. canis antigens induced a robust activation on this subset, contributing to the immune responses elicited in the experimental model for T. canis-associated visceral larva migrans syndrome. Data analysis demonstrated that, during murine T. canis infection, eosinophils from peripheral blood, spleen, and bone marrow presented upregulated expression of CD69/MHC-II/CD80/CD86. As opposed to splenic and bone marrow eosinophils, circulating eosinophils had increased expression of activation markers upon T. canis infection. The enhanced connectivity between eosinophils and T-cells in T. canis-infected mice in all three compartments (peripheral blood, spleen, and bone marrow) also supports the hypothesis that eosinophils may adopt a role during T. canis infection. Moreover, in vitro T. canis antigen stimulation resulted in activation and upregulation of co-stimulatory-related molecules by bone marrow-derived eosinophils. Our findings are evidence of activation and upregulation of important activation and co-stimulatory-related molecules in eosinophils and suggest a reshape of activation hierarchy toward eosinophils during experimental T. canis infection.

Eosinophils are multifunctional cells that have cytotoxic proinflammatory activities and stimulate CD4+ T-cells in experimental models of allergy and parasitic infections. Eosinophils, when exposed to antigens, are activated, expressing the CD38/CD69 molecules and exhibited increased expression of major histocompatibility complex (MHC-II), CD80 and CD86, suggesting they play a role upon Toxocara canis antigen stimulation. In the present study, we evaluated the profile of eosinophils using conventional and image flow cytometry upon experimental T. canis infection. T. canis antigens induced a robust activation on this subset, contributing to the immune responses elicited in the experimental model for T. canis-associated visceral larva migrans syndrome. Data analysis demonstrated that, during murine T. canis infection, eosinophils from peripheral blood, spleen, and bone marrow presented upregulated expression of CD69/MHC-II/CD80/CD86. As opposed to splenic and bone marrow eosinophils, circulating eosinophils had increased expression of activation markers upon T. canis infection. The enhanced connectivity between eosinophils and T-cells in T. canis-infected mice in all three compartments (peripheral blood, spleen, and bone marrow) also supports the hypothesis that eosinophils may adopt a role during T. canis infection. Moreover, in vitro T. canis antigen stimulation resulted in activation and upregulation of co-stimulatory-related molecules by bone marrow-derived eosinophils. Our findings are evidence of activation and upregulation of important activation and co-stimulatory-related molecules in eosinophils and suggest a reshape of activation hierarchy toward eosinophils during experimental T. canis infection.

Oral tolerance is defined as a state of systemic hyporesponsiveness to an antigen that has been previously administered by the oral route. Many factors affect oral tolerance induction; some of them related to antigen, and some related to the animal. The age of the animal is one of the most important factors that affect oral tolerance as ageing brings many alterations in immune responses. Herein, we demonstrated that both the oral tolerance and pattern of immune reactivity triggered in early life were kept up to 15 months regarding the magnitude of antibody production, cell proliferation and cytokine profile when compared to immune responses induced in old mice. Therefore, our results corroborate with a promising proposal for prevaccination during childhood and young age, and a booster in older age, to make sure that the primary immunization in early life is not lost in aged individuals.

Ageing is associated with several alterations in the immune system. Our aim in this study was to compare the development of immunity to Schistosoma mansoni infection in young versus aged C57Bl/6 mice using the liver as the main organ to evaluate pathological alterations and immune responses. In the acute phase, young mice had large liver granulomas with fibrosis and inflammatory cells. Chronic phase in young animals was associated with immunomodulation of granulomas that became reduced in size and cellular infiltrate. On the other hand, aged animals presented granulomas of smaller sizes already in the acute phase. Chronic infection in these mice was followed by no alteration in any of the inflammatory parameters in the liver. In concert with this finding, there was an increase in activated CD4+ T, CD19+ B and NK liver cells in young mice after infection whereas old mice had already higher frequencies of activated B, NK and CD4+ T liver cells and infection does not change these frequencies. After infection, liver production of inflammatory and regulatory cytokines such as IFN-gamma, IL-4 and IL-10 increased in young but not in old mice that had high levels of IL-4 and IL-10 regardless of their infection status. Our data suggest that the unspecific activation status of the immune system in aged mice impairs inflammatory as well as regulatory immune responses to S. mansoni infection in the liver, where major pathological alterations and immunity are at stage. This poor immune reactivity may have a beneficial impact on disease development.

Immunological alterations associated with aging (immunosenescence) do not represent a simple unidirectional decline in all functions but develop as a complex remodeling of the immune system, involving multiple reorganization and developmentally regulated changes. In general, most data available about aging were obtained at particular age intervals and most of them come from Caucasian individuals from either Europe or the United States. Here, we report the frequencies of major lymphocyte subsets in healthy Brazilian individuals from 2 distinct geographic regions (Southeast and South) at several age intervals spanning a lifetime period (0–86 years). Overall, we demonstrated that changes in the frequencies of cells related to both innate and adaptive immunity clearly occur with aging in these individuals. These changes were not progressive and equally steady for all cell populations tested but instead showed an oscillatory or rhythmic behavior that was distinctive of each population at different age intervals. We also observed that abrupt changes in the frequencies of immune cells may occur in healthy individuals over 75 years old, suggesting there is an impaired flexibility of the immune system at late stages of life to sustain homeostasis via immune mechanisms. We presented reference ranges for healthy Brazilian individuals at all ages. The knowledge of these parameters in further detail will allow interventions to optimize immune function in advanced age and to improve the quality of life in the elderly.

Summary There has been no systematic study of the immune response of individuals aged over 60 years living in Schistosomiasis mansoni-endemic areas, although senescence is reportedly associated with susceptibility to infection and progressive decline in immune function. We have shown previously, in two endemic areas in Minas Gerais, Brazil, that the frequency of individuals aged over 60 years with chronic schistosomiasis is no longer negligible. Moreover, several elderly individuals who have always lived in these endemic areas stay protected from infection. An important question for studies of ageing and disease control in developing countries is which differences in the immunological profile of these negatively tested (non-infected) individuals can account for their resistance to either infection or reinfection. We show, in the present study, that non-infected (negative) elderly individuals develop innate immune mechanisms of protection that replace the age-associated decline in T cell function. Non-infected elderly individuals from endemic areas of schistosome infection present an increase in the frequency of the natural killer (NK) CD56low subset of NK cells expressing Toll-like receptors (TLR)-1, -2, -3 and -4 as determined by flow cytometry analysis. In addition, the proportion of dendritic cells expressing TLR-1 is elevated as well as the frequency of monocytes expressing TLR-1 and -4. These results suggest that TLR expression by cells of the innate immune system may be related to the negative status of infection in some elderly individuals who are constantly exposed to S. mansoni. Developing mechanisms of protection from infection may represent a biomarker for healthy ageing in this population.

BACKGROUNG: Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection withSchistosoma mansoniin older individuals.Aim: Herein we study the influence of immunological alterations brought about by senescence in the course of schistosomiasis.Materials and methods: Individuals 10-95 years of age, from both sexes, from an endemic area forS. mansoniinfection were matched by intensity of infection as measured by egg counts. We analyzed, as a parameter, cytokine expression by lymphocytes and natural killer cells afterin vitrostimulation with soluble egg antigen and soluble worm antigen using flow cytometry.Results: We demonstrated that the frequency of CD16+interferon-γ (IFN-γ)+natural killer cells in negative individuals over the age of 70 years is significantly higher than in positive individuals afterin vitrostimulation withS. mansoniantigen extracts. The frequency of these cells is increased in all individuals over the age of 50 years and only declines in positive individuals after 70 years of age. Analysis of either CD4?or CD8?cells after antigen stimulation show no significant increase in frequency of IFN-γ in negative or in positive individuals of this age group, suggesting that the effect on CD16+cells is not T-cell dependent.Conclusion: Since production of IFN-γ has been related to resistance to schistosome infection, our data suggest that age-associated changes in CD16+cells may play a role in controlling infection intensity in the elderly inS. mansoniendemic areas of Brazil.

In the present review we address oral tolerance as an importantbiological phenomenon and discuss how it is affected by aging. Otherfactors such as frequency of feeding and previous digestion of theantigen also seem to influence the establishment of oral tolerance. Wealso analyze immunoglobulin isotypes of specific antibodies formedby tolerant and immunized animals of different ages submitted todifferent conditions of oral antigen administration. Isotypic patternswere studied as a parameter for assessing the pathways of B and T cellinteractions leading to antibody production. Correspondence A.M.C. FariaDepartamento de Bioquimica eImunologia, ICB, UFMGAv. Antonio Carlos, 662731270-901 Belo Horizonte, MGBrasilPresented at the InternationalMeeting on Cytokines, Angra dosReis, RJ, Brasil, November 24-28,1996.Research supported by FAPEMIG(No. 2501/96), PRPq and CNPq(No. 53.0349/93-0).Received September 4, 1997Accepted November 6, 1997 Key words • Oral tolerance • Aging • Isotypes •

The study population comprised HNSCC patients, risk-positive controls (tabagism and alcoholism habits), and risk-negative controls (without risk factors). Significant increases in the activation status of CD4(+)and CD8(+) T-cells, and higher migration potentials of lymphocytes were observed in HNSCC patients compared with control groups. Although decreased frequency of CD19(+)-B lymphocytes was observed in HSNCC patients, a higher percentage of HLA-DR(+)CD19(+)-B lymphocytes was detected in these individuals as compared with other evaluated groups. Metastasis and tumor grading were the major pathological parameters associated with significant alterations in the expression of activation molecules on circulating CD4(+) and CD8(+) T-cells. A reduced frequency of CD38-expressing CD8(+) T-cells was the most relevant biomarker associated with HNSCC aggressiveness. Performance analysis suggested a cut-off point for the CD8(+)CD38(+)/CD8(+) T-cell ratio of 7.0 for segregating patients according to tumor grading. In contrast, a higher proportion of CD8(+)CD54(+)/CD8(+) T-cells could represent a relevant biomarker associated with metastasis in HNSCC patients, and performance analysis suggested a cut-off point for the CD8(+)CD54(+)/CD8(+) T-cell ratio of 30 for segregating patients according to absence or presence of metastasis. The results obtained can increment immunological aspects of HNSCC and provide tools for the determination of cut-off scores of clinically relevant immunophenotypic prognostic biomarkers.

In this study, 395 volunteers were enrolled to investigate the seroprevalence of hepatitis C virus, the immunological and the alanine aminotransferase (ALT) biomarkers amongst hemodialysis patients, living in Manaus, Brazil. An overall seroprevalence of 13.9% was found in the hemodialysis patients. Analysis of seroconversion patterns demonstrated that most patients with HCV seroconverted up to 10 years following the first hemodialysis session. Anti-NS5 antibody was detectable in 60.4% of patients with HCV. A lower percentage of circulating CD3+ and CD4+ T-cells was found in patients seronegative for HCV, whereas a higher frequency of CD8+ T-cells was the hallmark of patients with HCV. An overall low activation state of monocytes and eosinophils were observed in hemodialysis patients. In contrast, a higher frequency of activated neutrophils was observed in patients with HCV, selectively in the NS5+ subgroup. All hemodialysis patients had a higher percentage of activated lymphocytes, with the higher activation state in patients with NS5− reactivity. Higher ALT levels were observed in patients with HCV, especially in the NS5+ subgroup. Interestingly, the ALT levels were correlated negatively with the lymphocyte activation state, selectively in the NS5− subgroup, suggesting a protective role of these activated lymphocytes in patients with HCV. These findings reinforce the importance of the transmission of HCV among hemodialysis patients, suggesting that apart from the HCV screening, the serological and ALT biomarkers may represent important predictors of morbidity and/or mortality among patients undergoing hemodialysis. J. Med. Virol. 81:1220–1231, 2009. © 2009 Wiley-Liss, Inc.

Senescence is characterized by several alterations in the immune system. Such modifications can be found in lymphoid organs as well as in the cellular components of the immune system. Several reports have suggested that immune dysfunction can affect both T and B cells, but T cells have been shown to be more susceptible to the effects of aging. B cell function may also be altered with reduction in germinal center formation, antibody response, and affinity maturation of antibodies. Herein we showed that although antigen-specific antibody response to a soluble antigen declines in 18-month old mice, total levels of serum antibodies as well as frequencies of spleen and bone marrow antibody-producing cells are increased in aged mice. In addition, proliferative response of non-stimulated spleen T cells from aged mice were augmented and insensitive to increasing doses of concanavalin A stimulation as compared to young mice that showed a typical dose-dependent response to mitogen stimulation in vitro. These data suggest that the higher activation mode of B and T cells in senescent mice is a result of an increased frequency of cells committed to previous antigenic experiences and with poor ability to respond to novel antigenic challenges.

There has been no systematic study of the immune response of individuals over 60 residing in areas endemic for Schistosoma mansoni infection although senescence is reportedly associated with susceptibility to infection and progressive decline in immune function. We have shown previously, in two endemic areas in Minas Gerais, Brazil, that the frequency of individuals over 60 with chronic schistosomiasis is no longer negligible. Several aging-related immunological alterations are already described in medical literature, mostly in the T-cell compartment. Since aging is associated with a decline in T-cell function, it is not surprising that individuals over 60 would be more susceptible to infection. However, not all aged individuals in endemic areas have high intensity of infection; some of them display a negative stool-screening test for the presence of schistosome eggs and low levels of serum antibodies reactive with S. mansoni antigens indicating they are not infected. Non-infected, negative individuals may develop compensatory mechanisms to cope with immune dysfunction and to generate protective responses against the constant threat of infection in these areas. Herein, we reviewed previous reports from our group showing that two mechanisms contribute to distinguish between infected and egg negative aged individuals. First, egg negative aged individuals develop innate immune responses to replace the decline in T-cell function that is observed with aging. Second, chronically activated regulatory T cells, that may impair protective immune responses, are more vigorous in infected aged individuals. We propose that egg negative individuals may be considered as an example of healthy aging in areas endemic for infectious disease.

A imunosenescência têm sido bem descrita em humanos e em uma variedade de espécies animais apresentando grande influência nas alterações funcionais do sistema imune que podem ser observadas tanto em órgãos linfóides, quanto nos componentes celulares do sistema imunológico. Foi demonstrado, por exemplo, alterações no fenótipo, repertório e ativação dos linfócitos, bem como no perfil de citocinas produzido por essas células. Existe, também uma forte associação entre resistência a infecções e reinfecções por parasitos helmínticos Schistosoma sp. e senescência. Na esquistossomose humana, por exemplo, a intensidade de infecção aumenta muito nas duas primeiras décadas de vida. A partir dos 30 anos de idade, esses mesmos indivíduos apresentam um declínio progressivo na intensidade da infecção que poderia ser devido à presença de mecanismos imunomoduladores. É uma doença crônica e se sobrepõe ao processo de envelhecimento. Nesse estudo, estudamos a influência das alterações imunológicas que ocorrem durante a senescência na esquistossomose humana. Indivíduos entre 10-95 anos de idade foram divididos em 4 grupos (10-24; 25-49; 50-69 e 70-95) de acordo com a intensidade da infecção em função dessa categoria (>100 ovos/g fezes), de ambos os sexos, moradores de área endêmica. Indivíduos que se mostraram negativos para ovos no exame de fezes pertencentes às mesmas faixas etárias descritas acima foram considerados nosso grupo controle. Nós analisamos, por citometria de fluxo, o perfil de síntese de citocinas por leucócitos do sangue periférico (células NK, linfócitos B, TCD4 e TCD8) após incubação in vitro de 5 horas com meio de cultura ou com os antígenos (SEA ou SWAP). Ao analisarmos os leucócitos totais do sangue periférico observamos, na cultura não estimulada, que o envelhecimento está associado ao aumento do percentual de IL-10 por leucócitos do sangue periférico em indivíduos idosos negativos e infectados, sugerindo um aumento na capacidade de modular a infecção maior que os indivíduos jovens. Além disso, também observamos paralelo ao aumento de IL-10, o aumento no percentual de IL-2 por esses leucócitos nos indivíduos infectados mais idosos (70-95 anos), sugerindo o aumento da reatividade celular ou apoptose das células. O perfil de síntese de citocinas por células NK, linfócitos B, TCD4 e TCD8, não estimulados, mostrou-se também bastante alterado com o envelhecimento. Nós observamos que, na idade jovem, há uma grande participação dos linfócitos T CD8+ caracterizado pelo aumento IL2+,IFN- +,IL-4+. Com a infecção, esse perfil muda, levando à diminuição dessas células positivas para IL-2 e IL-4, mas mantendo alto o percentual de células positivas para IL-10 e IFN- . Com o envelhecimento, observamos um perfil diferente. Existe uma grande contribuição de células T CD4+ caracterizado pelo aumento de células IL-10+ e IFN- +. Com a infecção, evidenciamos uma forte contribuição de ambas as subpopulações de linfócitos. Ocorre a diminuição de células T CD4+IL-10+ e IFN- + e o aumento de células CD4+IL-2+. Com relação aos linfócitos T CD8+, ocorre uma leve diminuição de células IL-4+ e IFN- + e um aumento de células CD8+ IL-10+ nessa faixa etária. Ao estimularmos a cultura de células com antígenos solúveis do ovo (SEA) ou antígenos solúveis do verme adulto (SWAP), os indivíduos idosos infectados (70-95 anos) mostraram um aumento no percentual de células CD16+IFN + que não foi observado em indivíduos negativos idosos (70-95 anos) e, uma diminuição no percentual de linfócitos B positivos para IL-10. Os resultados mostram que as diferenças se localizam nos polos extremos da vida. Os indivíduos adultos entre 25 e 69 anos apresentam padrões relativamente estáveis de síntese de citocinas. No entanto, diferenças marcantes nos padrões de citocinas positivas principalmente para células CD4+, CD16+ e CD8+ foram observadas em indivíduos negativos e infectados acima de 70 anos de idade. Esses dados sugerem fortemente que as alterações imunológicas encontradas estão relacionadas ao processo do envelhecimento. Além disso, a manutenção do percentual elevado de IL10 (mesmo que sintetizado por diferentes populações celulares) nos indivíduos infectados idosos provavelmente está diretamente relacionada à indução de mecanismos imunomoduladores típicos da fase crônica da infecção. Podemos dizer que o envelhecimento tem um forte efeito no percentual de citocinas e na imunidade a infecção pelo S. mansoni. The immunosenescence have been well described in humans and in a variety of animal species presenting large influence on the immune system functional changes which can be observed both in lymphoid organs and in cell components of immune system. It was demonstrated, for example, changes on the phenotype, repertoire and lymphocyte activation, as well as on the cytokine profile produced by this cells. There are also a strong association between the resistance to Schistosoma sp. helminthic infection and reinfection and senescence. In human schistosomiasis, for example, the worm burden increase in the two first decades of life. These same individuals, from the age of 30, show a progressive decline in the intensity of infection that could be due to the presence of immunomodulatory mechanisms. Schistosomiasis is a chronic disease and overlap to the aging process. This study, we assess the influence of the immunological changes that occur during senescence in human schistosomiasis. Individuals between 10 and 95 years old, of both gender, living in endemic area, were segregated in four groups of age (10-24; 25-49; 50-69 e 70-95). In each group, the subjects were categorized according the worm burden in either no eggs in faeces or more than 100 eggs/g of faeces. Individuals that presented no egg in faeces exam belonging to the same age group, described above, were considered our control group. We analyzed, with flow cytometry, the cytokine profile produced by periferic blood leucocytes (NK cells, B lymphocytes, T cells CD4+ and T cells CD8+) after 5 hours of in vitro incubation with either no stimuli or specific antigen stimulation (SEA or SWAP). When we analyzed the total leucocytes of periferic blood, we observed, in non-stimulated culture, that aging is associated to the increase of the frequency of leucocyte producing IL-10 from elderly infected and not infected, suggesting a greater ability to modulate the infection than young subjects. Moreover, we also observed, together to the increased of IL-10, the increase on the frequency of IL-2 in the leucocytes from older infected individuals (70 to 95 years old), suggesting the gain on the cellular reactivity or cell apoptosis. The cytokine profile produced by NK cells, B lymphocytes, T cells CD4+ and T cells CD8+, not stimulated, shows also very altered with aging. We observed that, in younger ages, there are a strong participation of the T CD8 lymphocytes characterized by the increase of IL2+,IFN- +,IL-4+ cells. With infection, this profile changes, taking a decrease of this IL-2 and IL-4 positive cells, but keeping the high percentage of IL-10 and IFN- positive cells. With aging process, we observed a different profile. There is a important contribution of the TCD4 cells characterized by the increase of IL-10+ e IFN- + cells. In the infection context, we noted a strong contribution of both the subpopulation of lymphocytes. It occurs a decrease of T CD4+IL-10+ and IFN- + cells and the increase of CD4+IL-2+ cells. Regarding to the TCD8+ lymphocytes, occurs a slight decrease of IL-4+ and IFN- + cells and an increase of the CD8+ IL-10+ cells in this age. With either the SEA-stimulation or SWAP-stimulation, the infected elderly (70 to 95 years old) showed an increase on the CD16+IFN + cells percentage that was not observed in negative elderly (70 to 95 years old), and, a decrease on the B cells percentage IL-10 positives. The results shows that the differences are located in the extremes of lifetime. The adults subjects between 25 and 69 years old presents stables pattern of cytokine synthesis. However, outstanding differences on the positive cytokine pattern to CD4+, CD16+ and CD8+ cells were observed in negative and infected individuals over 70 years old. This data strongly suggest that the immunological changes found are aging-related. In addition, the maintenance of the high percentage of IL-10 (even that produced by different cells populations) in the elderly infected individuals probably is directed related to the induction of immunomodulatory mechanisms typical of the chronic phase of infection. We can say that aging has a strong effect on the percentage of cytokine and on the immunity to the S. mansoni infection.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Tolerância oral é definida como um estado de hipo-reactividade sistémica frente a um antigénio que foi previamente administrado por via oral. Muitos fatores afetam a indução de tolerância oral, alguns deles relacionados com o antígeno, alguns relacionada com o animal. A idade do animal é um dos fatores mais importantes que afetam a indução de tolerância oral como o envelhecimento, que induz muitas alterações na resposta imune. A tolerância oral é mantida durante um longo período de tempo. Nosso estudo mostrou que tanto a tolerância oral, bem como a reatividade imune é mantida até um ano e meio e que essa manutenção pode ser visto em muitos aspectos da resposta imune em camundongos idosos que tiveram contato prévio com o antígeno quando jovem. Observou-se a manutenção da tolerância oral por meio da resposta humoral, após vários desafios com a Ova (p

B6D2F1 mice, which are very susceptible to tolerance induction by a single gavage with 20 mg of ovalbumin (Ova) at age 8 weeks, become less susceptible at age 25 weeks and totally refractory at age 70 weeks. However, 70-week-old mice may be rendered tolerant by repeated ingestion of Ova. Mice orally exposed to Ova at age 8 weeks remain tolerant at age 70 weeks. The isotypic pattern of anti-Ova antibodies formed by orally-tolerant and normal mice after immunization is similar and all isotypes are equally suppressed by oral tolerance. In old mice, oral exposures to Ova alone triggered an early transient antibody response; some of these responding animals were, nevertheless, tolerant to subsequent parenteral injection of Ova in adjuvant.

Background Immunosenescence is associated with several changes in adaptive and innate immune cells. Altered cytokine production is among the most prominent of these changes. The impact of age-related alterations on cytokine global profiles produced by distinct populations of leukocytes from healthy Brazilian individuals was studied. We analysed frequencies of cytokine-producing lymphocytes and innate immune cells from individuals at several ages spanning a lifetime period (0–85 years). Results Healthy adult individuals presented a balanced profile suggestive of a mature immune system with equal contributions of both innate and adaptive immunity and of both categories of cytokines (inflammatory and regulatory). In healthy newborns and elderly, innate immune cells, especially neutrophils and NK-cells, contributed the most to a balanced profile of cytokines. Conclusions Our results support the hypothesis that ageing is not associated with a progressive pro-inflammatory cytokine production by all leukocytes but rather with distinct fluctuations in the frequency of cytokine-producing cells throughout life. Electronic supplementary material The online version of this article (doi:10.1186/s12979-017-0084-5) contains supplementary material, which is available to authorized users.

Submitted by Jonathan Sousa de Almeida (jonathan.sousa@ufma.br) on 2022-08-03T09:52:38Z No. of bitstreams: 1 ALICEDESÁFERREIRA.pdf: 2533196 bytes, checksum: 0e20bf8c1e0d06803accc5c41b2ea824 (MD5) Made available in DSpace on 2022-08-03T09:52:38Z (GMT). No. of bitstreams: 1 ALICEDESÁFERREIRA.pdf: 2533196 bytes, checksum: 0e20bf8c1e0d06803accc5c41b2ea824 (MD5) Previous issue date: 2022-05-27 FAPEMA Introduction: COVID-19 is a disease caused by the highly infectious SARS-CoV-2 virus, leading to thousands of infected in a few days. An important finding in patients affected with COVID-19 is the change in hematological parameters and increased serum concentration of inflammatory cytokines, such as interleukin 6 (IL6), especially in severe cases of the disease. This study aimed to characterize hematological and inflammatory parameters in people affected by COVID-19 and to analyze the predicting power of biomarkers for the severity of the disease. Methods: This is a translational study with adult patients, positive for SARS- CoV-2 and living in a region of the Legal Amazon (São Luís/MA) from which sociodemographic data (age, gender, race/color, marital status, place of origin), health (molecular test result for COVID-19, place of hospitalization – infirmary or intensive treatment unit, oxygen saturation, discharge - hospital discharge or death) and laboratory discharge (hcomplete emogram, C Reactive protein - PCR, ferritin. In addition, inflammatory parameters (Neutrophil-Lymphocyte-Lymphocyte Relationship - RNL and Neutrophil- Platelet Relationship - RNP) were performed and the serum concentration of Pro- Inflammatory Cytokines was determined [Interleukin 6 (IL-6), Tumor Necrosis Factor Alpha (TNF-alpha), Interferon Alpha-2 (IFN-alpha 2), Interleukin 12p40 (IL-12p40), Interferon Gamma (IFN-Gamma), Beta Tumor Necrosis Factor (TNF-Beta), Interleukin 18 (IL-18), Interleukin IL-2R alpha (IL-2R alpha) and Interleukin IL-16 (IL-16)]. The participants were divided into a control group and according to the severity of the disease (moderate COVID-19 and severe COVID-19), which was determined by the place of hospitalization (infirmary or ICU) associated with oxygen saturation or need for mechanical ventilation. The data were analyzed using the software statistical program GraphPad Prism version® 8 and IBM SPSS version 24, with significance level of 0.05. Results: The number of total leukocytes (7598.51±3530 versus 13085±7985), neutrophils (5349.18±3565 versus 21910.75±6808), RNL (6.13±6.94 versus 15.86±25.53) and serum CRP concentration (4.47±4.77 versus 8.67±7.72) had higher averages in the group with severe COVID-19, with statistical significance (p 0.93, IL-16 presented AUC of 0.740, with a cutoff point > 33.55 and IFN-Alpha2 showed an AUC of 0.727, with cutoff point > 3.06 demonstrating to be good predictors of covid severity. Conclusion: This study demonstrated that laboratory parameters such as the number of total leukocytes, neutrophils, RNL, PCR, as well as pro-inflammatory cytokines IL-6, IL-16 and IFN-Alfa2 can predict the severity of COVID-19 and may thus be laboratory biomaracators of great help in the clinical management of the patient. Introdução: A COVID-19 é uma doença causada pelo vírus SARS-CoV-2, altamente infeccioso, levando a milhares de contaminados em poucos dias. Um achado importante nos pacientes acometidos com a COVID-19 é a alteração em parâmetros hematológicos e elevação da concentração sérica de citocinas inflamatórias, como a interleucina 6 (IL6), sobretudo em casos graves da doença. Este estudo objetivou caracterizar parâmetros hematológicos e inflamatórios em pessoas acometidas por COVID-19 e analisar o poder de predição desses biomarcadores para a gravidade da doença. Métodos: Trata-se de um estudo translacional com pacientes adultos, positivos para SARS-CoV-2 e residentes em uma região da Amazônia Legal (São Luís/MA) dos quais coletou-se dados sociodemográficos (idade, sexo, raça/cor, estado civil, local de origem), hospitalares (resultado do teste de molecular para COVID-19, local de internação – enfermaria ou unidade de tratamento intensivo, saturação de oxigênio, desfecho – alta hospitalar ou óbito) e laboratoriais (hemograma completo, proteína C Reativa - PCR, ferritina sérica). Além disso, realizou-se o cálculo de parâmetros inflamatórios (Relação Neutrófilo-Linfócito – RNL e Relação Neutrófilo- Plaquetas - RNP) e determinou-se a concentração sérica de citocinas pró-inflamatórias [Interleucina 6 (IL-6), Fator de Necrose Tumoral Alfa (TNF-alfa), Interferon Alfa-2 (IFN- alfa2), Interleucina 12p40 (IL-12p40), Interferon Gama (IFN-Gama), Fator de Necrose Tumoral Beta (TNF-Beta), Interleucina 18 (IL-18), Interleucina IL-2R alfa (IL-2R alfa) e Interleucina IL-16 (IL-16)]. Os participantes foram divididos em grupo controle e de acordo com a gravidade da doença (COVID-19 moderada e COVID-19 grave), o que foi determinado pelo local de internação (enfermaria ou UTI) associado a saturação de oxigênio ou necessidade de ventilação mecânica. Os dados foram analisados utilizando-se o software programa estatístico GraphPad Prism® versão 8 e IBM SPSS versão 24, com nível de significância de 0,05. Resultados: O número de leucócitos totais (7598.51±3530 versus 13085±7985), neutrófilos (5349.18±3565 versus 21910.75±6808), a RNL (6.13±6.94 versus 15.86±25.53) e a concentração sérica de PCR (4.47±4.77 versus 8.67±7.72) tiveram maiores médias no grupo com a COVID-19 grave, com significância estatística (p 0,93, a IL-16 apresentou AUC de 0,740, com ponto de corte > 33,55 e o IFN-Alfa2 mostrou uma AUC de 0,727, com ponto de corte > 3,06 demonstrando serem bons preditores de gravidade da COVID. Conclusão: Este estudo demonstrou que parâmetros laboratoriais como o número de leucócitos totais, de neutrófilos, a RNL, a PCR, bem como as citocinas pró- inflamatórias IL-6, IL-16 e IFN-Alfa2 foram capazes de predizer a gravidade da COVID-19 podendo assim, serem biomarcadores laboratoriais de grande auxílio no manejo clínico do paciente.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais O envelhecimento saudável, acompanhado de um remodelamento bem sucedido do organismo e do sistema imune, representa um paradigma para as sociedades modernas. Entender quais são as funções que deterioram e as que podem compensá-las, assim como conhecer quais os marcadores biológicos (imunológicos, genéticos e epigenéticos) são determinantes para o avanço salutar da idade, pode permitir intervir de forma a promovê-lo. Assim, neste estudo, buscamos analisar os fatores imunes relacionados ao tecido adiposo (adiponectina, resistina e leptina) que possam se associar ao “envelhecimento saudável”. Trata-se de um estudo transversal com 54 indivíduos saudáveis de ambos os sexos, divididos em 3 grupos: 19-60 anos (n= 18); 60-75 anos (n=19); > 75 anos (n=17). As concentrações de adiponectina, leptina e resistina no soro foram determinadas pela técnica de ELISA (Kit R&D System DuoSet). Os achados descritos apontam para o declínio significativo dos níveis séricos de leptina em indivíduos maiores de 75 anos, independente do estado nutricional, o que não se repetiu para a resistina e a adiponectina. Mais pesquisas são necessárias para elucidar a influência exercida pelo tecido adiposo nas funções homeostáticas do sistema imune envolvidas no envelhecimento. Healthy aging, accompanied by a successful remodeling of the body and the immune system, represents a paradigm for modern societies. Understand haw body functions deteriorate and how the organism compensate, as well as know which biological markers (immunological, genetic and epigenetic) are determinants for healthy in advancement age, may allow intervention to promote better life span. In regard of that, this study, proposed to analyze the immune factors released by adipose tissue (adiponectin, resistin and leptin) that may be associated with "healthy aging". This is a cross-sectional study with 54 healthy individuals of both sex, divided into 3 groups: 19-60 years (n = 18); 60-75 years (n = 19); > 75 years (n = 17). The concentrations of adiponectin, leptin and resistin in serum were determined by ELISA (R & D System DuoSet Kit). The findings indicate a significant decline in serum levels of leptin in individuals older than 75 years, independent of nutritional status, which was not repeated for resistin and and resistin in serum were determined by ELISA (R & D System DuoSet Kit). The findings indicate a significant decline in serum levels of leptin in individuals older than 75 years, independent of nutritional status, which was not repeated for resistin and adiponectin. Further research is needed to elucidate the influence exerted by adipose tissue on the homeostatic functions of the immune system involved in aging.

O câncer é uma enfermidade crônica degenerativa que apresenta um crescimento desordenado (maligno) de células, podendo espalhar-se (metástase) para outras regiões do corpo. O processo de carcinogênese ou oncogênese compreende desde alterações precoces no DNA até a formação do tumor, podendo acarretar a destruição do organismo hospedeiro, de maneira lenta e progressiva. Como em outras neoplasias malignas, o câncer de boca tem o seu desenvolvimento estimulado pela interação de fatores ambientais, agentes cancerígenos ou carcinógenos e fatores do hospedeiro como idade, raça, sexo e herança genética. Alguns agentes externos também são fatores predisponentes ao desenvolvimento do câncer como exposição à radiação solar, e tabagismo e etilismo crônicos. As infecções oportunistas da cavidade bucal são primariamente causadas por fungos do gênero Candida e ocorrem frequentemente nesse grupo de pacientes. Considerando os aspectos relacionados à presença de fungos na cavidade bucal e seu discutível papel no câncer, o objetivo deste trabalho foi verificar o potencial agressor das leveduras do gênero Candida entre os diferentes pacientes que apresentam câncer orogástrico, incluindo aspectos relacionados ao diagnóstico da neoplasia bucal, a produção de proteinase e fosfolipase, e a capacidade de adesão das leveduras, à terapia antifúngica e à população celular envolvida na resposta imune do paciente. Foram incluídos neste estudo 59 pacientes com diagnóstico clínico confirmado para o câncer e presença de Candida spp. e 34 indivíduos do grupo controle. Para confirmação do diagnóstico de câncer, fragmentos de tecido foram submetidos às análises cito e histológicas. As amostras de swabs orais foram semeadas em ágar Sabouraud dextrose, para posterior identificação das espécies. As leveduras foram identificadas por testes presuntivos através da produção de pigmento no meio de CRHOMagarCandida, características morfológicas e teste confirmativo através da espectrometria de massa MALDI-TOF. No grupo com câncer foram identificadas 32 (51,6%) amostras como Candida albicans, 4 (6,5%) como C. tropicalis, 9 (14,5%) como C. glabrata, 4 (6,5%) como C. krusei, 8 (12,9%) como C. parapsilosis e 5 (8%) como C. lusitaneae. Para o grupo controle 14 (66,7%) foram identificadas como C. albicans, 5 (23,8%) como C. parapsilosis,1 (4,8%) como C. krusei e 1 (4,8%) como C. glabrata. As leveduras foram também avaliadas quanto à expressão de fatores de virulência como a produção de proteinase e fosfolipase, a sua capacidade de adesão, e quanto ao perfil de susceptibilidade aos antifúngicos, comumente utilizados na clínica médica. Também foi feita uma avaliação no soro dos pacientes com câncer oro-gástrico e grupo controle para que fosse determinado o perfil de resposta imune nos indivíduos envolvidos no trabalho. Tanto o exame histopatológico que é o método mais utilizado para a análise de lesões suspeitas de malignidade, quanto o exame citopatológico, considerado uma forma de diagnóstico alternativo, demonstraram sensibilidade de 100% em todas as amostras analisadas, sendo este método uma ferramenta promissora para a realização do diagnóstico de câncer de boca. Cinquenta e nove por cento dos indivíduos do grupo controle e 85% dos pacientes com câncer orogástrico apresentaram levedura na cavidade oral sendo a espécie Candida albicans a mais prevalente com 66,7% nos indivíduos do grupo controle e 48,4% nos pacientes com câncer. As leveduras recuperadas dos indivíduos com câncer foram mais aderentes que os isolados provenientes do grupo controle. Quanto à produção de fosfolipase, foi observado uma maior produção, tanto para as amostras recuperados dos indivíduos do grupo controle quanto para os pacientes com câncer, com 61,9% e 51,6% respectivamente. Já para a proteinase, foi observada maior produção nas amostras proveniente dos pacientes com câncer com 41,9%. Para grupo controle, somente 4,8% apresentaram esta característica. Diante do teste de susceptibilidade à drogas antifúngicas, a maiorias das amostras para os dois grupos que fizeram parte do estudo apresentaram sensibilidade a todos os antifúngicos testados sendo que, as amostras do grupo controle apresentaram maior sensibilidade dos que as amostras dos pacientes com câncer. Por fim, quanto ao perfil imunológico avaliado a partir do soro dos pacientes com câncer e grupo controle, foi observado que nos pacientes com câncer, houve um aumento estatisticamente significativo das citocinas IL-2, IL-10, TNF- IFN-e IL-17 em relação aos indivíduos do grupo controle (saudáveis), mostrando haver uma alteração sistêmica nestas citocinas inflamatórias entre os indivíduos com câncer oro gástrico. Cancer is a chronic degenerative disease that presents a disordered growth of cells and may spread to other body regions. The process of carcinogenesis and oncogenesis ranges from early changes in DNA to tumor formation, which may cause the destruction of the host organism, slowly and progressively. As in other malignant neoplasms, oral cancer has its development stimulated by the interaction of environmental factors, carcinogens or carcinogens and host factors as age, race, sex and genetic inheritance. Some external agents are also predisposing to cancer development factors such as exposure to solar radiation, as well as smoking and chronic alcoholism. Opportunistic infections of the oral cavity are primarily caused by fungi of the genus Candida and occur frequently in this group of patients. Considering the aspects related to the presence of fungi in the oral cavity and its questionable role in cancer, the aim of this study was to determine the potential aggressor of Candida species among different patients who had orogastric cancer, including issues related to the diagnosis of neoplasia buccal, antifungal therapy and cell population involved in the immune response of the patient. To confirm the diagnosis of cancer, tissue fragments were subjected to cytological and histological analyzes. Both histopathologic as cytopathologic tests, considered a form of alternative diagnosis, showed sensitivity of 100% for all samples analyzed. In this study 59 patients with clinical diagnosis for cancer and presence of Candida spp. and 34 control subjects without cancer were included. Oral swabs samples of individuals were seeded in Sabouraud Dextrose Agar for identification of species. Yeasts, after screening with pigment production in the middle of CRHOMagarCandida were identified by morphological tests through microcultive and confirmatory testing by MALDI-TOF. Fifty (85%) of patients with cancer oro-gastric and 20 (59%) of the control subjects showed yeast in the oral cavity. Candida albicans was the most prevalent species, both in patients with cancer (48.4%) and in control subjects (66.7%). Among the 50 cancer patients who had yeast in the oral cavity, in eight of these, two different Candida species and in two, three different strains were isolated, totaling 62 samples. Of the 20 control subjects, positive for Candida in the oral cavity, one had two species, totaling 21 isolates. In the group with cancer 32 (51.6%) samples were identified as Candida albicans, 4 (6.5%) as C. tropicalis, 9 (14.5%) as C. glabrata, 4 (6.5%) as C. krusei, 8 (12.9%) as C. parapsilosis and 5 (8%) as C. lusitaniae. In the control group 14 yeast (66.7%) were identified as C. albicans, 5 (23.8%) as C. parapsilosis, 1 (4.8%) as C. krusei and 1 (4.8%) as C. glabrata. Yeasts were also assessed for the expression of virulence factors such as the production of proteinase and phospholipase, their adhesion ability, and as to the susceptibility to antifungal agents, commonly used in medical clinical profile. Among the samples of Candida spp. isolated, 54.2% and 32.5% produced phospholipase and proteinase, respectively. Isolates from patients with cancer showed higher proteinase production (41.9%) than those isolated from the control group (4.8%). Samples of Candida isolated from the oral cavity of patients with cancer had higher adhesion to buccal epithelial cells (BEC) than those of the oral cavity of people without alteration of the oral mucosa (p = 0.05). Candida species from cases with cancer showed higher sensitivity to isoconazole, voriconazole, ketoconazole and amphotericin B antifungals while the samples of Candida tropicalis were resistant to fluconazole. The samples of the control group demonstrated the sensitivity to all the antifungals tested. In this study 100% of individuals who had oral cancer were smokers and chronic alcoholics. An assessment was also performed, to be given the profile of immune response in the serum of individuals with oro-gastric cancer and the control group. In cancer patients there was a statistically significant increase in IL-2, IL-10, TNF, IFN- and IL-17 in the control group suggesting that there was a systemic change in these inflammatory cytokines in patients with neoplasia.