Nonapoptotic and extracellular activity of granzyme B mediates resistance to regulatory T cell (Treg) suppression by HLA-DR-CD25hiCD127lo Tregs in multiple sclerosis and in response to IL-6.
Taken together, our data indicate an important role for miR26a in maintaining the Th17 and Treg cell balance in MS that involves repression of IL6 expression.
The aim of this study was to investigate the vitamin D effects on the expression level of IL-6 and IL-17A in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients.
Furthermore, the production of IL-17 and IL-6 by MS-derived T cells was directly related with neurological disability (EDSS score), and the release of these cytokines was less sensitive to glucocorticoid inhibition in MS patients than in control group, mainly after DA addition.
In this review, we further discuss evidence for B cell and Ig contribution to human MS and NMO pathogenesis, pro-inflammatory and regulatory B cell effector functions, impaired B cell immune tolerance, the B cell-fostering microenvironment in the CNS, and B cell-targeted therapeutic interventions for MS and NMO, including CD20 depletion (rituximab, ocrelizumab, and ofatumumab), anti-IL6-R (tocilizumab), complement-blocking (eculizumab), inhibitors of AQP4-Ig binding (aquaporumab, small molecular compounds), and BAFF/BAFF-R-targeting agents.
Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell-driven pathogenesis in T cell-mediated autoimmune disease such as EAE and MS.
In the present study, we analyzed these polymorphisms, together with an additional polymorphism (-572 G>C) in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different -597 or -174 IL6 promoter alleles or genotypes.
To study the possible role of tumor necrosis factor-alpha G-308A, interleukin-6G-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.
The results corroborate a pro-inflammatory state in MS as reflected by high expression of IL-12, TNF-alpha and IL-6, although the extent of expression of TNF-alpha, IL-6 and IDO differs between strictly matched MS patients from different high-incidence areas.
The aim of this study was to investigate the possible influence of TNF-alpha (-308), TGF-beta (codons 10 and 25), IL-10 (-1082, -819, -592), IL-6 (-174) and IFN-gamma (+874) polymorphisms on susceptibility to multiple sclerosis (MS).
We have concluded that soluble proteins of TNF-alpha, IL-6 and sIL-6R gp80 assayed by monoclonal antibodies-based ELISAs could not serve as markers of the MS activity.
Future studies focusing on complex transcriptional interactions between the IL-6pr and 3' flanking region polymorphic sites will be necessary to determine the IL-6 haplotype influence on susceptibility to MS.
No association of serum levels of interleukin-6 and its soluble receptor components with a genetic variation in the 3'flanking region of the interleukin-6 gene in patients with multiple sclerosis.
Given the potential relevance of this animal model for multiple sclerosis (MS), it is possible that anti-IL-6 therapy may be useful in the prevention of relapses of MS.