Macrophage depletion decreases IgG anti-DNA in cultures from (NZB · NZW)F1 spleen cells by eliminating the main source of IL-6

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Abstract
SUMMARY: We have studied ihe rote of macrophages in the produclion of IgG anli-DNA autoanlibodies by (NZB × NZW)F1 tnice(B/W). One of the main features of the syslemic lupus cryibematosus(SLE)-like disease that aftects these mice, h ihe presence of circuialing IgG autoantibodies and immune complexes, which lead lo renal failure and death by the age of 8–9 months. IgG autoantibodies are produced without in vitro siimulallon by lolal spleen eells from these miee when they reach tbe age of 6 monlhs. We have demonstrated ihat IL-6 increases ihe production of IgG autoantibodies in cultures of splenic purified B cells from the old B/W miee. The aim of this study was to show the involvement of macrophages in the production of IL-6 and consequently in the produclion of IgG anti-DNA antibodies in ritro. We show thai elimination of the macrophages by different treatments led to reduction of the content of IL-6 in ihe supernalants as well as of IgG anti-DNA autoantibodies. Addition of fresh, splenic or peritoneal macrophages restored the produclion of autoantibodies in macrophage-depleted cultures from old B/W miee. There were no ditferences in the capacity of IL-6 produelion between macrophages from old or young B/W miee. but an imporiani difference was observed between peritoneal and splenic maerophages, where the former produced mueh higher levels ol IL-6, and eonsequently were more potent inducers of IgG autoantibodies. The present results reinforee Ihe role of macrophages and lL-6 in Ihe production of IgG anti-DNA autoantibodies in B/W mice. The implieations of these results in the pathogenesis of the disease are discussed.