The predominance of beta (CC) chemokine transcripts in idiopathic inflammatory muscle diseases.
Cytokines and chemokines that upregulate major histocompatibility complex class I antigens, recruit lymphocytes, and enhance T-cell-mediated myotoxicity may be important in the pathogenesis of dermatomyositis and polymyositis. We searched for cytokine and chemokine transcripts in inflammatory muscle specimens from 14 newly diagnosed or treated patients. Control specimens from six patients without inflammatory muscle disease were analyzed for transcripts of interleukins-1 beta, -2, -4, -6, -10, and -15, and interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta 1, macrophage inflammatory proteins-1 alpha and -1 beta (MIP-1 alpha, MIP-1 beta), and the chemokine "regulated on activation, normally T expressed and secreted" (RANTES). Surprisingly, the proinflammatory and lymphocyte cytokines were detected only sporadically in myositis muscle specimens, and their presence did not correlate with disease activity or treatment status of the patient. In contrast, MIP-1 alpha and MIP-1 beta were detected in 13 and 6 myositis biopsies, respectively, and RANTES, another beta (CC) chemokine, was detected in eight myositis biopsies. This study and other reports of low levels of acute-phase cytokines in myositis patients suggest that the proinflammatory cytokines do not play a major role in ongoing muscle damage. The CC chemokines studied here, in particular MIP-1 alpha, might contribute to ongoing muscle inflammation, and the pathogenesis of inflammation in myositis may follow a previously unrecognized pathway.
Adams
E M
EM
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kirkley
J
J
Eidelman
G
G
Dohlman
J
J
Plotz
P H
PH
D002478:Cells, Cultured; D018925:Chemokines / Q000032:analysis* / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D003882:Dermatomyositis / Q000276:immunology*; D006801:Humans; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D017285:Polymyositis / Q000276:immunology*; D014158:Transcription, Genetic
D018925:Chemokines; D018076:DNA, Complementary