Abstract
Oligoarticular juvenile idiopathic arthritis (oJIA) is an antigen-driven and lymphocyte-mediated disorder affecting the adaptive immune system. Auto reactive T cells produce pro-inflammatory cytokines as IFN-γ and IL-17. Failure of regulatory T cells leads to decreased production of anti-inflammatory IL-10 and results in the loss of immune tolerance. Therapeutic strategies suppress T cell dependent immune responses and consequently inhibit the process of inflammation. The aim of the study was to investigate the effect of T cell suppression on the cytokine network in oJIA patients. Therefore we examined the cytokine concentration after in vitro inhibition of T cells by cyclosporine and abatacept in patients with persistent oJIA and healthy control subjects. This single center cohort study consisted of oJIA affected children and control subjects. Cytokine profiles from cell culture supernatants were examined with multiplex fluorescent bead immunoassay by flow cytometry. High amounts of IL-17 were only observed in the collective of oJIA patients after T cell stimulation. Cyclosporine suppresses its concentration effectively. IL-2 and IFN-γ are present in both groups. We found IL-6 and TNF-α in high concentrations after T cell activation. While TNF-α concentration is suppressed by both drugs, IL-6 concentration remains high in oJIA patients. Concentrations of IL-4 and IL-10 were not found to be influenced in status of activation or suppression. In conclusion, the results of the present study imply that IL-17 is the crucial T cell cytokine in oligoarticular JIA. Only cyclosporine could inhibit the secretion of IL-17 effectively. IL-2 and IFN-γ are not specific for oligoarticular JIA. Both cytokines are found as well in healthy control subjects after T cell stimulation. Relevant pro-inflammatory macrophage cytokines in oligoarticular JIA are TNF-α and IL-6. T cell suppression by cyclosporine and abatacept inhibits TNF-α but not IL-6 effectively. Production of anti-inflammatory cytokines is not influenced by T cell suppression.
Highlights
Juvenile idiopathic arthritis (JIA) refers to a group of chronic childhood arthropathies of unknown aetiology which represents the most common rheumatic condition in children
Production of anti-inflammatory cytokines is not influenced by T cell suppression
We examined the presence of twelve cytokines in leukocyte culture supernatants of 10 Oligoarticular juvenile idiopathic arthritis (oJIA) patients as well as 15 healthy individuals by flow cytometry analysis
Summary
Juvenile idiopathic arthritis (JIA) refers to a group of chronic childhood arthropathies of unknown aetiology which represents the most common rheumatic condition in children. There exist two hypotheses for the development of autoimmune phenomena in oJIA: Massa et al reported that T cell cross-recognition (molecular mimicry) of exogenous and self HLA-derived antigens generates an abnormal regulatory circuit which maintains and expands T cells, which may participate in autoimmune inflammation by generation of pro-inflammatory cytokines [5] Another hypothesis is that auto-antigens derived from cartilage and other joint-related tissue, such as aggrecan, fibrillin and matrix-metalloproteinase 3 (MMP3), may be able to activate auto-reactive CD4+ T cells, including Th1 and Th17 cells which are correlated with autoimmune symptoms of oligoarticular JIA [4] [6] [7]. IL-17 is able to maintain disease activity independent of TNF-α [14]
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