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Background: Chronic rhinosinusitis (CRS), as an inflammatory airway disease, could be a risk factor for COVID-19 patients. This study aimed to investigate the frequency and severity of symptoms of COVID-19 in patients with CRS and to assess the association between the status of CRS symptoms and the quality of life (QoL) of the patients., Methods: In this observational and cross-sectional study, 207 adult CRS patients participated. The patients, who presented the symptoms of COVID-19, were examined by taking the reverse transcription-polymerase chain reaction test. A questionnaire was completed by each patient, regarding their demographic and clinical data. In addition, the GA 2 LEN and Sino-Nasal Outcome Test (SNOT-22) standard questionnaires were used to identify the comorbid allergic condition and QoL of CRS patients., Results: The frequency of patients with COVID-19 was 25 (12.1%) of which 22 were treated as outpatients, 2 of them admitted in wards and 1 at intensive care unit. The severity of hyposmia in the patients was 2 (8%) as mild, 5 (20%) moderate, and 11 (72%) as anosmia. The most common allergic and underlying comorbid diseases were allergic rhinitis (88%) and thyroid disorders (28%). Further, the average SNOT-22 score in 4 SNOT-22 domains (nasal, otologic, sleep, and emotional symptoms) was significantly decreased in CRS patients after a period of one year since the pandemic started (40.1 ± 18.0 vs. 46.3 ± 17.7; P < .0001)., Discussion: This study showed a low frequency of COVID-19 in patients with CRS and about the same rate of infection positivity in the general population; therefore, we concluded that CRS could not be considered as a risk factor for COVID-19. Interestingly, the lower average score of SNOT-22 after one year of the pandemic in the patients with CRS confirmed the necessity for performing the standard health protocols by the patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Allergic diseases could play a role of a predisposing factor for coronavirus disease 2019 (COVID-19). The aim of this study was to investigate allergic comorbidity and its association in COVID-19 patients., Methods: Demographic data, clinical manifestations, laboratory reports, and radiologic findings, together with underlying comorbidity of patients, were studies. Allergic diseases were identified by using the standard GA 2 LEN questionnaire. The severity of COVID-19 was assessed by a visual analog scale (VAS) and an intensive care unit (ICU) report., Results: Out of 400 COVID-19 patients admitted in the hospital, 158 (39.5%) presented with different allergic diseases, and a reverse association was observed between having allergic comorbidity and severity of COVID-19 infection (P = 0.005, relative risk = 0.96; 95% Confidence Interval (95% CI): 0.77-1.19). The respective frequency of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS), atopic dermatitis, chronic urticaria, and food or drug allergy was 7.3%, 16%, 1.8%, 5%, 10% and 13.3%. Significantly, only AR was reversely associated with the severity of COVID-19 (P = 0.02, relative risk = 0.45; 95% CI: 0.77-1.19). Additionally, 43% of the patients presented hypoxemia, and 93.5% had chest CT scan involvement. Interestingly, patients with allergic diseases had significantly lower hypoxemia and chest CT involvement as compared with non-allergic patients (P = 0.002 and 0.003, respectively)., Conclusion: The results of this study established that allergic diseases were not determined to be a predisposing factor for the severe acute respiratory syndrome (SARS) due to coronavirus 2 (SARS-CoV-2) infection. Significantly, AR patients developed mild clinical manifestations of COVID-19 and admitted to ICU as compared to non-AR patients., Competing Interests: There were no conflicts of interest in this study.

Allergic rhinitis (AR) is a prevalent disease affecting the quality of life of patients throughout the world. This study aimed to assess the prevalence of AR and its association with chronic rhinosinusitis (CRS) in the adult population living in Bushehr, southwestern part of Iran. In this population-based study, a total of 5420  individuals aged 15-65 years were selected through a multi-stage, cluster, random sampling method from which 5201 of them completed the Global Allergy and Asthma Network of Excellence (GA2LEN) questionnaire (Response rate=96.1%). The prevalence of AR, based on Allergic Rhinitis and Its Impact on Asthma (ARIA) classification (mild or moderate; intermittent or persistent) was calculated and the association of AR and CRS was evaluated using a multiple logistic regression model. The overall prevalence of AR was 28.8%, and for the intermittent and persistent AR were 25.9% (out of which 81.34% were moderate to severe) and 74.1% respectively. Moreover, the prevalence of AR was significantly higher in health workers and smokers (p=0.002 and p<0.001, respectively). Furthermore, an association was found between AR and CRS (p<0.001, aOR: 4.68, 95%CI: 4.07-5.39), and also, between the persistent AR and CRS as compared with the intermittent (p<0.001, aOR: 4.21, 95%CI: 3.40-5.22). The present study showed that the prevalence of AR in Bushehr (Southwestern part of Iran) was significantly high. In addition, the results indicated a strong association between AR and CRS, especially in individuals with moderate to severe persistent AR.

Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: An award was given to Iraj Nabipour by “Novo Nordisk Pars” (The Best Innovator of Diabetes in Iran 2013). For the remaining authors none were declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Asthma is recognized as a major public health concern in the world. The aim of this investigation was to evaluate the prevalence of asthma by using the Global Allergy and Asthma Network of Excellence (GA 2 LEN) questionnaire and examine its association with chronic rhinosinusitis, in the province of Bushehr, Southwestern of Iran., Methods: In a cross-sectional, population-based study, a total of 5420 invited individuals, aged 15-65, were selected through a multi-stage, stratified, cluster random sampling and from which 5201 completed the GA 2 LEN questionnaire (response rate = 95.9%). The prevalence of asthma, current, and physician-diagnosed asthma were analyzed by using sex and age groups and the association of asthma and chronic rhinosinusitis (CRS) was investigated using a multiple logistic regression model., Results: Based on the information from the GA 2 LEN questionnaire, the overall prevalence of asthma in the population under study was 10.0% (95% CI 9.2-10.8). Moreover, the prevalence of current asthma was 8.9% (95% CI 8.1-9.7). Further, the prevalence of current early, late-onset and physician-diagnosed asthma within the asthma group was 51.1% (95% CI 46.5-55.7), 48.9% (95% CI 44.3-53.5) and 3.9% (95% CI 2.1-2.5), respectively. Additionally, CRS was more frequent among the participants with asthma [(57.3%, OR = 2.3; 95% CI 2.1-2.5)], and there was a significant association between CRS and current, early and late-onset of asthma (P < 0.001; OR = 4.4, 3.2 and 6, respectively)., Conclusion: This large population study conducted in the southwestern part of Iran suggests that the prevalence of asthma is high. Moreover, the result of this study showed a strong association of asthma with CRS; also after adjusting for sex, age, educational level, and smoking., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: T regulatory cells (Tregs) are known to negatively control immune response. The frequency of these cells was inversely correlated with clinical outcomes of breast cancer. CD19 + CD24 hi CD38 hi cells also play a critical role in inflammation and autoimmune disease. However, their function in tumor immune response is less studied. In this study we aimed to determine the role of CD19 + CD24 hi CD38 hi cells and some other clinicopathological variables in increasing the proportion of Tregs in breast cancer patients., Methods: We selected 47 patients with invasive ductal breast carcinoma and 50 healthy controls and obtained their blood samples., Results: The proportion of circulating CD4 + CD25 + Foxp3 + Tregs and CD19 + CD24 hi CD38 hi cells was significantly increased in breast cancer patients. We also found that increased proportion of Tregs in breast cancer is correlated with HER2 amplification, advanced clinical stages, serum TGF-β1 and increased CD19 + CD24 hi CD38 hi cells in the peripheral blood., Conclusion: Altogether, our data suggest that as much as Tregs, CD19 + CD24 hi CD38 hi B cells could also have a part in the suppression of immune response in breast cancer.

Despite the recent increases in fungi-induced allergic diseases, there is no report yet in the region of the Persian Gulf on concentration levels of fungi in relationship with health state. Therefore, our aim was to measure fungi prevalence as well as to evaluate the relationships between air- and dust-borne fungal genera and allergic diseases. A matched case-control study was carried out including 45 allergic cases and 45 age- and gender-matched controls for each individual. Indoor and outdoor dust and indoor air samples were collected from participant homes during May to October 2015. A Quick Take 30 Pump and sterile wet swab were used to determine fungal types and their amounts in the air (CFU/m 3 ) and dust (CFU/100 cm 2 ) samples, respectively. A significant reverse association was found between indoor dust-borne Alternaria and asthma (Odds ratio (OR) = 0.14, 95% CI = 0.02-0.86). Contrarily, increased levels of indoor air-borne Aspegillus fumigatus (OR = 2.00, 95% CI = 0.37-10.55) and Alternaria (OR = 3.00, 95% CI = 0.34-25.83) were correlated with asthma development. Also, correlation analysis showed a significant relation between indoor air-borne Penicillium levels and reactivity to skin prick test in asthmatic patients (p = 0.04). Our findings support the notion that fungal exposures can either cause or prevent the development of allergic diseases. Accordingly, appropriate measures should be taken for a better management of fungi-induced allergic diseases.

Toll-like receptors (TLRs), a family of pattern recognition receptors expressed on many cell types of innate immunity, recognize the pathogen-associated molecular patterns of microbes. The hygiene hypothesis suggests that a reduced microbial exposure in early childhood increases the susceptibility to allergic diseases due to deviation in development of the immune system. TLRs are key roles in the right and healthy direction of adaptive immunity with the induction of T-helper 2 toward Th1 immune responses and regulatory T cells. TLR ligand CpG-ODN-based immunomodulation is independent of allergen and it mainly affects innate immune system. While, CpG-oligodeoxynucleotide-based vaccination is allergen specific and induces adaptive immune system. The use of agonists of TLR9 in two distinct strategies of immunotherapy, immunomodulation and vaccination, could be presented as the curative method for the treatment of allergic diseases.

ZAP-70 deficiency is a rare autosomal recessive form of combined immunodeficiency (CID) characterized by selective absence of circulating CD8 T cells with low, normal, or increased CD4 T cells in peripheral blood. Up to now, 14 unique mutations in the ZAP70 gene have been identified in patients with ZAP-70-related CID. We present a 3-year-old boy with a history of recurrent bacterial infections and autoimmunity. Initial laboratory findings showed a normal total lymphocyte count, but low levels of CD8 and CD4 T cells and an abnormal lymphocyte proliferation response. Immunoglobulin levels were normal, but the specific antibody response was impaired. Whole exome sequencing revealed a mutation within the kinase domain of ZAP-70. ZAP-70 deficiency should be considered in infants and young children with recurrent bacterial infections, in spite of having palpable lymph nodes, a notable thymus shadow, and a normal total lymphocyte count.

The potential link between infection with Chlamydia pneumoniae or Helicobacter pylori and osteoporosis has not been investigated in population-based longitudinal studies. A total of 250 healthy postmenopausal women who participated in a prospective cohort study were evaluated for IgG antibodies directed against C. pneumoniae and H. p ylori, osteoprotegerin (OPG), the receptor activator of nuclear factor kappa B ligand (RANKL), CrossLaps, and osteocalcin. Bone mineral density (BMD) was measured at the femoral neck and lumbar spine at baseline and at follow-up 5.8 years later. There were no significant differences in age-adjusted bone turnover markers, OPG, RANKL, the RANKL/OPG ratio, and BMD between the C. p neumoniae and H. p ylori IgG seropositive and seronegative subjects (P > 0.05). Neither C. p neumoniae nor H. p ylori IgG seropositivity was associated with age-and body mass index-adjusted BMD at the femoral neck and lumbar spine or bone loss at the 5.8-year follow-up. In logistic regression analysis, neither C. p neumoniae nor H. p ylori IgG seropositivities predicted incident lumbar or spine osteoporosis 5.8 years later. In conclusion, neither C. p neumoniae nor H. p ylori IgG seropositivity was associated with bone turnover markers, the RANKL/OPG ratio, BMD, or bone loss in postmenopausal women. In addition, chronic infection with C. p neumoniae or H. p ylori did not predict incident osteoporosis among this group of women.

Human epidermal growth factor receptor-2 is an important and prognostic factors and one of the most targeted proteins in breast cancer's therapy. There is no globally accepted method for determining its status. Here, we aimed to evaluate the immunohistochemistry method validity in predicting HER-2 status by Fluorescence in situ hybridization method and investigate some clinicopathological variables association with HER-2 amplification. A total of 190 HER-2 2+ and 3+ by immunohistochemistry (IHC) invasive breast cancer cases were enrolled in this study. Fluorescence in situ hybridization (FISH) was performed for these cases using FDA criteria and the association between clinicopathological variables and HER-2 status evaluated. Study consisted of 190 invasive breast cancer patients (160 HER-2 2+ and 30 HER-2 3+). HER-2 FISH amplification according to FDA criteria was found 27.5% (44/160 patients) in HER-2 2+ patients and 83.3% (25/30 patients) in HER-2 3+ patients. Tumors with HER-2 amplification were more likely to be ER-negative (51.0% vs 31.2%, p = 0.013) and PR-negative (52.9% vs 27.0%, p < 0.001). This study showed that immunohistochemistry is not a good method for evaluating HER-2 status and decision-making about trastuzumab therapy even with 3+ score patients. However, this result may not be too strong for IHC 3+ cases due to the limited number of these patients in this study., (© 2016 APMIS. Published by John Wiley & Sons Ltd.)

Background: Patients with β-thalassemia major (TM) develop iron overload through increased iron absorption and transfusional therapy and it's the most important complication of TM. Thalassemia is common in coastal regions and lands with low altitudes. The aim of this study is to determine the effect of high and low altitude on serum ferritin and treatment requirement in two groups of β-thalassemia major (TM) patients., Subjects and Methods: Patients were divided into two groups, the first group (No: 50) living at sea level (in the port of Bushehr, Iran) and the second group (No: 40) living at the altitude of 2061 m (in the city of Shahrekord, Iran). All patient's clinical history, blood transfusion and laboratory tests including complete blood count and hemoglobin electrophoresis were reviewed., Results: There were no significant difference in ferritin levels, transfusion period and diabetes incidence of the two cities patients (P>0.05). Patient's cardiac function and liver condition were significantly better in patients of Bushehr (P<0.05). Patients under 20 years in Bushehr were less splenectomized in comparison with Shahrekord (P<0.05)., Conclusion: Our result showed that some of clinical manifestations of patients in low altitude such as cardiac and liver condition were better. But it did not affect ferritin level probably due to transfusion and chelating therapy. Totally patients of Bushehr had better conditions and had longer survivals.

Purpose: The main objective of the Bushehr Elderly Health Programme, in its first phase, is to investigate the prevalence of cardiovascular risk factors and their association with major adverse cardiovascular events., Participants: Between March 2013 and October 2014, a total of 3000 men and women aged ≥ 60 years, residing in Bushehr, Iran, participated in this prospective cohort study (participation rate=90.2%)., Findings to Date: Baseline data on risk factors, including demographic and socioeconomic status, smoking and medical history, were collected through a modified WHO MONICA questionnaire. Vital signs and anthropometric measures, including systolic and diastolic blood pressure, weight, height, and waist and hip circumference, were also measured. 12-lead electrocardiography and echocardiography were conducted on all participants, and total of 10 cc venous blood was taken, and sera was separated and stored at -80 °C for possible future use. Preliminary data analyses showed a noticeably higher prevalence of risk factors among older women compared to that in men., Future Plans: Risk factor assessments will be repeated every 5 years, and the participants will be followed during the study to measure the occurrence of major adverse cardiac events. Moreover, the second phase, which includes investigation of bone health and cognition in the elderly, was started in September 2015. Data are available at the Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran, for any collaboration., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aeroallergens continue to have a key role in the pathogenesis of asthma and allergic diseases and have recently received increased attention in medical research throughout the world. The prevalence of aeroallergens vary in different regions, depending on the type of climate. The aim of the present study was to determine prevalence of the sensitivity to aeroallergens among patients with asthma and allergic rhinitis (AR), based on skin prick test (SPT) reactivity in the province of Bushehr, Iran. In this cross-sectional study, 743 patients were enrolled. The participants had asthma and AR and reacted to at least one allergen with SPT. Skin prick test with standard extracts including house dust mites (HDMs), animal dander, molds and pollens were performed on patients according to the herbal geography of the area. The male to female ratio and mean age of the patients were 1.03 and 27.6± 15.4 year, respectively. Out of 567 patients with AR, the common aeroallergens were HDMs (88.5%), molds (82.9%), animal dander (79.5%), weeds (77.6%), trees (75.5%) and grass pollen (71.5%). Moreover, among 176 patients with asthma, the prevalence of aeroallergens were HDMs (90.5 %), molds (80.7%), animal dander (77.5%), weeds (73.3%), trees (73.3%) and grass pollen (67.9%). The sensitivity to animal dander, Chenopodium album and Russian thistle pollens were significantly associated with the severity of AR. Moreover, sensitivity to animal dander such as cat and feather of birds, cockroach, Bermuda grass and Chenopodium album pollens were significantly associated with the severity of asthma. The results of this study revealed that HDM was the most common sensitizing aeroallergen in patients with asthma and AR. Molds and animal dander as indoor allergens were also common aeroallergens. We suggest that the hot weather and ambient humidity in the region may be the main cause of the change in the pattern of SPT reactivity.

Concerns have been raised about the adverse impact of dusty air pollution (DAP) on human health. The aim of this study was to find the association between dusty air pollution based on air quality index (AQI) and the risk of allergic diseases in southwestern provinces of Iran, with assessing cytokine profiles and lymphocyte immunophenotypes.In this case control study 148 individuals participated. The sampling was done in hazardous condition (AQI>300) as the case and clean air (AQI<50) as the control. We measured cytokine production by using ELISA method and phenotypes of T-lymphocytes (CD4+ and CD8+), CD19+ B-lymphocytes, CD25+, CD4+ CD25+ cells by FACSort flow cytometer.The mean serum level of IL-4 (33.4 ± 2.9 vs 0.85 ± 0.65 pg/dl) and IL-13 (15.1 ± 4.4 vs. 0.12 ± 0.7 pg/dl) in the subjects exposed to ambient DAP was increased significantly compared to the individuals in the clean air condition. Also, CD19+ B-lymphocytes (12.6 ± 4.9 vs 8.9 ± 3.2%) and CD4+ CD25+ cell count (13.6 ± 4.6 vs 7.7 ± 3.8%) in peripheral blood were increased significantly in subjects exposed to ambient DAP compared with the controls.The result of our study suggested that ambient DAP affected immune system in a way that might lead to allergic diseases in the population.

Objective: Studies determining the relationship between serum vitamin D status and childhood asthma have yielded controversial results. Findings indicated that vitamin D deficiency is associated with asthma and airway hyper responsiveness. The aim of this study was to assess the relationship between serum vitamin D status and childhood asthma., Methods: Data were obtained from 200 asthmatic children (age 3-12 years) and 200 healthy controls. Serum levels of 25(OH) vitamin D, total IgE, calcium, phosphorus, parathormone (PTH) and eosinophil count were measured in both asthmatic children and healthy controls. Also, the mean values of 25(OH) vitamin D were compared with asthma symptom severities., Findings: There was a significant decrease in the concentration of serum 25(OH) vitamin D in the asthmatic patients as compared with the controls (20.34±2.8 vs 25.39±4.1 ng/mL, 95%CI: 1.46-3.86, P=0.01). Out of total asthmatic subjects, 40 (20%) were vitamin D sufficient, 48 (24%) were insufficient, and 112 (56%) were deficient. Total IgE concentration was also significantly higher in asthmatic patients having vitamin D deficiency (132.4±20.1 IU/ml, 95%CI: 1.38-3.75, P=0.03). Comparing asthmatic patients with healthy controls, odds of having vitamin D level less than 20ng/mL was 2.47., Conclusion: Our findings suggest that vitamin D deficiency or insufficiency may be positively related to the prevalence of asthma in children.

Asthma and allergic diseases present a major health burden. Information on the prevalence of these diseases indicates that these diseases are increasing in various parts of the world. It was hoped that this study would be helpful to health system policy-makers in planning allergy prevention programs in the region.The prevalence of asthma and allergic diseases and relation between the various risk factors involved were assessed among schoolchildren in the city of Bushehr, Iran. The ISAAC Phase I and III questionnaires were completed by parents of 1280 children aged 6-7 years and self-completed by 1115 students aged 13-14 years.The prevalence of atopic eczema, allergic rhinitis and asthma among 6-7 year-old students were 12.1%, 11.8% and 6.7%, respectively. While, the prevalence of these diseases among 13-14 year-old students were found to be 19%, 30% and 7.6%, respectively. There was an association between asthma and allergic rhinitis as well as eczema (p<0.05). Consumption of fast food as a risk factor was significantly associated with asthma (p=0.03).The prevalence of asthma and allergic diseases was high among schoolchildren in the city of Bushehr, Iran. Also an association was observed between the fast food consumption and asthma.

Although the pathological relationship between parathyroid and thyroid diseases is common, an association between parathyroid adenoma and thyroid cancer is rare. Concomitant thyroid cancer in patients with primary hyperparathyroidism (pHPT) has been reported at varying frequencies. WE present here a 23-year-old man who had papillary thyroid carcinoma in the right thyroid lobe and a parathyroid adenoma in the left thyroid lobe, which were confirmed surgically.

Background: Renal artery stenosis (RAS) has been increasingly recognized in the recent years, especially in patients with coronary artery disease (CAD). RAS affects the patients with hypertension (HTN), but the exact prevalence is not known., Objectives: This study was performed to determine the prevalence and to identify the predictors of RAS in hypertensive patients undergoing coronary artery angiography., Patients and Methods: In a cross-sectional study from August 2008 to August 2009, 481 patients with HTN and suspected CAD underwent selective coronary and renal angiography for screening and predicting RAS. RAS was defined as a higher than 50% stenosis in the renal artery lumen. Multivariate analysis of factors associated with the presence of RAS were examined using a logistic regression model., Results: The mean ± standard deviation of age was 59.25 ± 10.81 years and 50.3% were men. According to angiographic data, 425 patients (88.4%) had CAD, while 56 (11.6%) had normal coronary arteries. RAS was seen in 94 (22%) patients with CAD. The multivariate logistic regression analysis identified only age (P < 0.001) and the number of significant coronary lesions (P < 0.001) as independent predictors of RAS. Gender, smoking, congestive heart failure, diabetes mellitus (DM), hyperlipidemia (HLP) and body mass index (BMI) were not independent predictors., Conclusions: This study suggests that in the management of patients with RAS, risk factors should most likely be considered as beneficial. In addition, the clinical and angiographic features are helpful in predicting its presence in elderly patients with CAD.

Allergic Rhinitis (AR) is one of the most common chronic diseases in the developed countries. This study was performed to investigate the effect of CpG-ODN in alteration of T-helper (Th)1/Th2 balance of patients with AR treated with intranasal corticosteroids (INCs) and antihistamines. Peripheral blood mononuclear cells (PBMCs) of 20 patients with AR were isolated before and after 45 days therapy. Cytokine production (IL-4, IL-10, IL-13, IFN-γ) and specific Ch.a IgE in response to CpG co-administration of natural chenopodium album (CpG/Ch.a) or recombinant Ch.a (CpG/rCh.a) allergen were investigated in supernatants.of cultured PBMCs using ELISA Intracellular IL-10 was also assessed in CD4+ cells using flow cytometry. Significant increase in production of IFN-γ and IL-10 and decrease in production of IL-4 were found in supernatants of cultured PBMCs activated with CPG/ch.a and CPG/rch.a. of both CpG/Ch.a and CpG/rCh.a compared to allergens alone, before and after therapy. After therapy, IFN-γ production with CpG/Ch.a was significantly increased in comparison with before (237 vs. 44 pg/ml, p=0.001). IFN-γ and IL-10 production with CpG/rCh.a was significantly increased after therapy compared to before (407.6 vs. 109 pg/ml, p=0.01 for IFN-γ; 171.7 vs. 52.6 pg/ml, p=0.008 for IL-10), whilst IL-4 was significantly decreased (2.1 vs. 5.8 pg/ml, p=0.02). Intracellular IL-10 expression was also significantly increased in response to either CpG/Ch.a or CpG/rCh.a that showed intracellular assay could be more sensitive than ELISA. Also, treatment with intranasal corticosteroids and antihistamines could enhance this CpG effect, in vitro.

Patients with allergic rhinitis (AR) show increased production of the Th2-related cytokines. Almost always, intranasal corticosteroid (INC) and antihistamine are used as routine therapy of AR. This study was performed to determine the in vitro secretion of cytokines profiles of PBMCs in patients with AR sensitive to Chenopodium album (Ch.a) pollens before and after treatment with INC (Fluticasone propionate) and oral antihistamine (Loratadine). PBMCs of 20 patients with AR, were tested in vitro for cytokine production. These cells were stimulated with natural or recombinant Ch.a. The levels of IL-4, IL-13 and IFN-, were measured in supernatants of cultured cell 96h after stimulation using ELISA. The PBMCs of 20 normal individuals were also similarly treared for comparison of results. The production of IL-4 by the patients' cells stimulated with either Ch.a or rCh.a was significantly higher than normal levels before therapy (p=0.04 and p=0.02, respectively). After therapy, a significant decrease in production of IL-4 and a significant increase in production of IL-10 were found in PBMCs stimulated with natural Ch.a, in comparison to the results before stimulation (p=0.03 for IL-4; p=0.04 for IL-10). Similarly, these results were seen in the production of IL-4 and IL-10 stimulated with rCh.a allergen after therapy in comparison to the results before stimulation (p=0.01 for IL-4; p=0.03 for IL-10). This study suggests INC (Fluticasone propionate) and oral antihistamine (Loratadine) have the capacity to inhibit the production of IL-4 and shift Th2/Th1 responses, probably due to increase the level of immunoregulatory IL-10. Therefore, it could be concluded that therapy with INC and antihistamine has pharmacologic and immunologic therapeutic effects on AR patients.