Defective spontaneous and bacterial lipopolysaccharide-stimulated production of interleukin-1 receptor antagonist by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus

Interleukin-1 receptor antagonist (IL-lra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-lra producing capacity of these cells. PMN and MNC at a concentration of 1 × 10⁶ cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-lra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-lra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 μg/ml) did not change the production of IL-lra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-lra producing capacity of PMN in seven active SLE on admission and after intensive immunosupprcssive treatment was measured. These results suggest that the defective IL-lra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.