Cytokines in the muscle tissue of idiopathic inflammatory myopathies: implications for immunopathogenesis and therapy

The inflammatory myopathies (IM), dermatomyositis (DM), polymyositis (PM) a nd idiopathic inclusion body myositis (IBM) are acquired immune-mediated my opathies. About their pathogenesis and etiology no definitive insights are available yet, Here we present a review of cytokine studies in IM, Combined with cellular immunohistochemical findings a model is presented describing a common mechanism of immune activation in IM. This model is based on a "h it" triggering local cytokine production with dominance of proinflammatory cytokines, like IFN-gamma and Th1-mediated activities. The altered Th1-Th2 balance necessitates detection of the anti-inflammatory arm of immune activ ation, which includes Th2-derived IL-4, IL-1, and Th3/Tr1 derived IL-10 and TGF-beta, Redirection of the ratio provides targets for novel immunotherap y by direct inhibition of the IFN-gamma-mediated Th1 response, stimulation of Th3/Tr1, or IL- 4-secreting Th2-cells, negative feedback inhibition with IFN-beta and IFN-gamma and inactivation of MHC molecules.