IMPAIRED PRODUCTION OF IL-12 IN SYSTEMIC LUPUS-ERYTHEMATOSUS - I - EXCESSIVE PRODUCTION OF IL-10 SUPPRESSES PRODUCTION OF IL-12 BY MONOCYTES

Interleukin 12 (IL-12) plays a crucial role in defensive immune respon ses, modulation of cytokine production and is involved in the pathogen esis of some autoimmune diseases, The authors investigated whether dec reased in vitro production of IL-12 occurs in systemic lupus erythemat osus (SLE), in which the cytokine secreting pattern is predominantly t ype 2, IL-12 production by SLE peripheral blood mononuclear cells (PBM C) was significantly impaired compared with normal PBMC, and this was not due to decreased numbers of monocytes, After depletion of non-adhe rent cells from PBMC, monocytes of SLE patients produced significantly less IL-12 than those of controls, but IL-12 levels in SLE and contro l non-adherent cell supernatants were not significantly different. Exo genous recombinant (r)IL-10 strongly inhibited IL-12 production by bot h SLE and normal PBMC and anti-IL-10 neutralizing antibody significant ly reversed the IL-12 deficiency of SLE PBMC and SLE monocytes, while not affecting normal PBMC, Recombinant interferon gamma (rIFN-gamma) c onsiderably enhanced IL-12 production in both SLE and normal PBMC, but it did not significantly reverse the inhibitory effect of rIL-10 on I L-12 production, IL-12 production was significantly lower in patients with active SLE than those in remission, These results suggest that SL E monocytes may be deficient in IL-12 production and that this is seco ndary to abnormal production of various cytokines, especially excessiv e production of IL-10. (C) 1998 Academic Press Limited.