Contribution of tumour necrosis factor α and interleukin (IL) 1β to IL6 production, NF-κB nuclear translocation, and class I MHC expression in muscle cells:: in vitro regulation with specific cytokine inhibitors

Objective: To evaluate the effect of tumour necrosis factor alpha (TNF alpha), interleukin ( IL) 1 beta, and their respective inhibitors the p75 TNF alpha soluble receptor (sTNFR) and the type II sIL1 beta R (sIL1 RII) on whole muscle and isolated myoblast activation. Methods: Normal muscle samples were stimulated for 7 days with TNF alpha alone or in combination with IL1 beta, and myoblasts from these samples for 48 hours. IL6 production was measured by ELISA. Nuclear translocation of NF-kappa B was analysed by immunofluorescent staining and class I MHC expression by FACS. Results: TNF alpha and IL1 beta induced IL6 production by normal muscle samples and myoblasts, the action of TNF alpha being more potent on muscle samples. Their soluble receptors ( 1 mu g/ml) decreased this production. Suboptimal concentrations of TNF alpha and IL1 beta induced NF-kappa B translocation. sTNFR markedly down regulated TNF alpha-induced translocation while sIL1RII was less potent on IL1 beta-induced activation. NF-kappa B translocation induced by the combination of optimal concentrations of TNFa and IL1b was completely inhibited by their soluble receptors. TNF alpha and to a lesser extent IL1 beta induced class I MHC expression by myoblasts and this effect was completely inhibited by their respective soluble receptors. Conclusion: These results suggest that TNF alpha and IL1 beta should be targeted for myositis treatment.