Cytokines in the muscle tissue of idiopathic inflammatory myopathies: implications for immunopathogenesis and therapy.
The inflammatory myopathies (IM), dermatomyositis (DM), polymyositis (PM) and idiopathic inclusion body myositis (IBM) are acquired immune-mediated myopathies. 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 "hit" triggering local cytokine production with dominance of pro-inflammatory cytokines, like IFN-gamma and Th1-mediated activities. The altered Th1-Th2 balance necessitates detection of the anti-inflammatory arm of immune activation, 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 immunotherapy 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.
Megens-de Letter
M A
MA
Department of Neurology, St. Elisabeth Hospital Tilburg, PO Box 90151, 5000 LC Tilburg, The Netherlands. megens-deletter@wxs.nl
Visser
L H
LH
van Doorn
P A
PA
Savelkoul
H F
HF
D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology*; D009220:Myositis / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D016207:Cytokines; D007166:Immunosuppressive Agents