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Association studies of proinflammatory and anti-inflammatory cytokines single nucleotide polymorphisms with multiple sclerosis (MS) in population with different ethnic background have shown inconsistent results. To study the possible role of tumor necrosis factor-alpha G-308A, interleukin-6 G-174C, interleukin-10 C-592A, C-819T, G-1082A, transforming growth factor (TGF)-beta (codons 10 and 25), and interferon-gamma T+874A polymorphisms in susceptibility to MS in Iranian population, DNA samples from 98 patients and 97 healthy controls were genotyped using polymerase chain reaction-sequence-specific primers. Analysis of the genotypes revealed a significant lower frequencies of tumor necrosis factor-alpha GA and TGF beta C/C G/G genotypes and higher frequency of TGF beta T/C G/C genotype in patients (P < 0.05). Our data suggest that these polymorphisms play a role in susceptibility to MS, which is possibly mediated by dysregulated production of these cytokines.

Experimental autoimmune encephalomyelitis (EAE) is an appropriate model for the study of the immunologic and pathologic mechanisms in multiple sclerosis (MS). According to the hygiene hypothesis, helminths can improve immunoregulation and have therapeutic effects on immune‐mediated diseases. In this study, we used Dicrocoelium dendriticum (Dicrocoeliidae, Platyhelminthes) eggs for the evaluation of their prophylactic and treatment effects on EAE disease. D. dendriticum eggs were extracted. Female C57BL/6 mice were immunized with the specific antigen MOG35−55, and then the egg extracts were utilized for prophylaxis and/or treatment. Clinical symptoms and other relevant parameters were assessed daily. The mRNA expression of transforming growth factor‐β (TGF‐β), interleukin‐10 (IL‐10), IL‐6, IL‐23 and IL‐17 were assessed with a real‐time polymerase chain reaction technique. Furthermore, secretion of TGF‐β and IL‐17 cytokines were determined by enzyme‐linked immunosorbent assay. Data indicated that clinical symptoms in prophylaxis and treatment groups were decreased significantly in comparison with the untreated control group (p <.001). Our results showed a significant decrease in IL‐17, as well as an increase in TGF‐β cytokine in the treatment group compared to the EAE control group (p <.01). Furthermore, in the prophylaxis and treatment groups, the mRNA expression of disease‐associated cytokines decreased and the mRNA expression of the anti‐inflammatory cytokines increased. In this study, the D. dendriticum egg ameliorates the clinical symptoms of the EAE model through the modulation of related cytokines of Th17 and Treg cells. Therefore, using this parasite egg could be a new treatment for MS. [ABSTRACT FROM AUTHOR]

Aims: This study aimed at investigating the impact of Dicrocoelium ova on experimental autoimmune encephalomyelitis (EAE) treatment in C57BL6 mice. Methods and Results: Twenty‐eight C57BL/6 mice were assigned into four groups as PBS, prophylaxis (P), treatment1 (T1) and treatment2 (T2). Prior to induction of EAE in prophylaxis group and on days 7 and 18 in T1 and T2 groups, respectively, Dicrocoelium eggs were injected intraperitoneally to each mouse. The clinical score, weight changes and incidence time of EAE were recorded. IFN‐γ and IL‐4 expression is quantified on spleen cells. Also, histopathological study by (H&E) and Toluidine‐Blue (TB), and Luxol Fast Blue (LFB) were performed. The data were analysed using SPSS version 21. Mean disease scores were significantly lower in P and T1 groups than the PBS group (P =.01). IFN‐γ was lower in P and T1 groups than the PBS group. The highest level of IL‐4 was observed in T1 group. The total number of neuroglia cells of corpus callosum was similar in all groups, but the density increased in T1 group compared to the PBS group (P =.03). Conclusions: Dicrocoelium eggs have a great potential to stimulate immunomodulation towards treatment of EAE during the initial phase. [ABSTRACT FROM AUTHOR]

Highlights • QS-21 adjuvant as the safest saponin among all of the saponins from the Quil A mixture provides the adjuvant properties needed to establish a mild relapsing-remitting EAE C57BL/6 mouse model. • Thermal hyperalgesia, a clinical manifestation of central neuropathic pain, was developed during the disease course with no severe motor impairment in the mice group immunized with the QS-21 adjuvant. • EAE induced by QS-21 adjuvant presents only severe neuroinflammation, but no significant demyelination in the white matter. • QT-0101 seems to be an appropriate adjuvant for vaccination of autoimmune diseases against auto-antigens. Abstract Background The majority of patients with multiple sclerosis (MS) suffer from central neuropathic pain (CNP). Using experimental autoimmune encephalomyelitis (EAE) model, only a few experiments were performed to assess pain behaviors in MS. To address this issue, complete Freund's adjuvant (CFA) was replaced with an acylated triterpene glycoside saponin adjuvant named quillaja saponin-21 (QS-21) to develop CNP in the EAE mouse model. The deacylated form of QS-21, named QT-0101, has been suggested to have an immunomodulatory effect. Thus, QT-0101 was used as a vaccine adjuvant to modulate the immune system against myelin oligodendrocyte glycoprotein (MOG35-55) antigen. Methods In this study, C57BL/6 mice, except for mice in the negative control (PBS) and MOG groups, were divided into three groups and immunized by MOG35-55 emulsified with CFA, QS-21, or QT-0101 adjuvants, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, through the Hot Plate test and the clinical signs, was assessed for 60 days after immunization. On days 21 and 60, mice were sacrificed and the frequency of TCD4+, TCD8+, IL-17+, IL-4+, and CD25+/FoxP3+ cells population in the total splenocytes population was assessed by flow cytometry. Infiltration of Leukocytes into the brain and demyelination of white matter were also evaluated by histopathologic studies. Results Our results revealed that unlike the MOG+QT-0101 group, the MOG+QS-21 and MOG+CFA groups represented clinical symptoms that mimic the mild relapsing-remitting and monophasic models, respectively. Thermal hyperalgesia, as a CNP clinical manifestation, developed in the bilateral hind paws in the MOG+CFA and MOG+QS-21 mice groups during the onset of neurologic deficits, but it is maintained until completion of the study only in MOG+QS-21 mice group. The frequency of TCD4+, TCD8+ and IL-17+ cells population in the MOG+QS-21 and MOG+CFA mice groups, as well as IL-4+ and CD25+/Foxp3+ cells population in the MOG+QT-0101 mice group, significantly increased in comparison with the PBS mice group. Infiltration of inflammatory cells increased significantly in the MOG+QS-21 and MOG+CFA mice groups compared with the PBS mice group. Demyelination of white matter was identified significantly only in the MOG+CFA mice group compared with the PBS mice group. Conclusion These results showed that QS-21 is a suitable adjuvant for the establishment of a mild relapsing-remitting EAE model for CNP development and open a new avenue to future pre-clinical and clinical research studies related to CNP treatment. Nevertheless, QT-0101 seems to have the potential to act as a vaccine adjuvant with immunomodulatory property against auto-antigens. [ABSTRACT FROM AUTHOR]