Abnormal IL-1 receptor antagonist production in patients with polymyositisand dermatomyositis

Objective To examine the relationship between serum levels of interleukin-1 receptor antagonist (IL-1Ra) and its gene expression in peripheral blood m ononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM). Methods IL-1Ra levels in sera from patients and supernatants of unstimulate d monocyte cultures were measured by enzyme-linked immunosorbent assay, Exp ression of IL-1Ra mRNA was analyzed by Northern blotting, and an 86-base pa ir variable repeat polymorphism in intron 2 of the IL-1Ra gene was determin ed by polymerase chain reaction. Results Serum IL-1Ra was significantly elevated in 27 patients with active- stage PM/DM when compared with levels in 16 patients with inactive-stage PM /DM and 19 normal controls. Serum concentrations of IL-1Ra were correlated with PM/DM disease activity. IL-1Ra mRNA was detected in freshly isolated P BMC from patients with active-stage PM/DM, but not in controls. Moreover IL -1Ra concentrations were increased significantly in unstimulated monocytes from patients with active-stage PM/DM compared with monocytes from normal c ontrols, However, there were no significant differences in IL-1Ra allele fr equencies between patients and normal controls. Conclusion Elevation of both IL-1Ra mRNA and protein in sera of patients wi th active-stage PM/DM suggest that higher levels of serum IL-1Ra may reflec t increased IL-1Ra production in myositis, and that IL-1Ra may regulate IL- 1-mediated muscle fiber damage in PM/DM.