Differential expression of chemokines in inflammatory myopathies

Abstract

Background: Chemokines represent a family of small-molecular-weight cytokines that recruit and activate inflammatory cells in response to inflammation. Invasion of cytotoxic memory T cells and macrophages in nonnecrotic muscle fibers characterizes polymyositis and sporadic inclusion body myositis. Dermatomyositis is a complement-mediated endotheliopathy. Elucidation of the mechanisms guiding lymphocyte diapedesis and trafficking could lead to selective therapeutic interventions.Methods: Immunoblots and multistep immunofluorescence studies with non–cross-reactive antibodies recognizing interleukin-8, monocyte chemoattractant protein-1 (MCP-1), MCP-3, TARC (thymus and activation regulated cytokine), and RANTES (regulated upon activation, normal T-cell expressed and secreted), using appropriate positive and negative controls. In situ hybridization was used to localize MCP-1 mRNA.Results: MCP-1 protein was strongly expressed on T cells and a subset of macrophages actively invading a proportion of the nonnecrotic muscle fibers in polymyositis and inclusion body myositis alike. Capillaries and arterioles in the vicinity of endomysial inflammatory foci were immunoreactive for MCP-1, with faint or no expression in unaffected parts of the tissue. By contrast, widespread and strong endothelial MCP-1 expression occurred on perifascicular and perimysial endothelia in dermatomyositis, also at sites remote from inflammatory infiltrates. In some control specimens, a subset of capillaries also expressed MCP-1, possibly reflecting a role of this chemokine in normal immune surveillance. MCP-1 mRNA was detected in scattered macrophages in each inflammatory myopathy. All other chemokines were absent.Conclusion: Chemokines are differentially expressed in the symptomatic stage of inflammatory myopathies. MCP-1 plays a major role in the myocytotoxicity in polymyositis and inclusion body myositis. MCP-1 may be induced by membranolytic attack complex binding to endothelial cells in dermatomyositis.