The role of cytokines, chemokines, and adhesion molecules in the pathogenesis of idiopathic inflammatory myopathies.
Cytokines, chemokines, and adhesion molecules are important mediators in chronic inflammation and in immune regulation. In idiopathic inflammatory myopathies (IIM), increased expression of proinflammatory cytokines particularly interleukin (IL)-1alpha and IL-1beta, tumor necrosis factor (TNF)-alpha and macrophage inflammatory proteins (MIP)-1alpha, as well as of the inhibitory cytokines transforming growth factor (TGF)-beta was observed in muscle. There was no difference in cytokine and chemokine pattern between polymyositis, dermatomyositis, and inclusion body myositis, which could indicate that similar pathogenetic mechanisms are involved in these subsets of myositis. A prominent finding of IL-1alpha expression in endothelial cells, both in patients with active inflammation and in patients with chronic persisting muscle weakness without inflammation, makes this an interesting molecule in understanding the mechanisms for the pathogenesis of muscle weakness. Involvement of the blood vessels in the pathogenesis of myositis was further supported by increased expression of adhesion molecules and by a phenotypical expression of endothelial cells, resembling high endothelium venules in all three subsets of IIM. The molecular studies to date indicate a role of the microvessels in the pathogenesis of IIM not only in DM, as was previously suggested, but also in PM and IBM. The studies also indicate that IL-1alpha could be a target molecule for new therapeutical interventions.
Lundberg
I E
IE
Department of Rheumatology, Karolinska Hospital, S-171 76 Stockholm, Sweden. Ingrid.Lundberg@medks.ki.se
D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000502:physiology*; D018925:Chemokines / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology; D009220:Myositis / Q000209:etiology / Q000276:immunology* / Q000473:pathology
D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1