HUMAN GLYCOPROTEIN HGP92 INDUCES CYTOKINE SYNTHESIS IN MOUSE MONONUCLEAR PHAGOCYTES

HGP92 has been shown to enhance in vitro and in vivo the bactericidal and tumoricidal activity of mouse macrophages. In this study we invest igated the effect of HGP92 on the accumulation of cytokine mRNA in mou se inflammatory, peritoneal macrophages and the monocytic cell line J7 74, HGP92 significantly enhanced the level of cytokine mRNA for IL-1 a lpha, IL-1 beta, IL-6, IL-10, IL-12, TNF-alpha and GM-CSF during the f irst 24 h of the incubation, This effect triggered by HGP92 was compar able to that obtained with lipopolysaccharide (LPS), which is a strong cytokine inducer. This accumulation of cytokine mRNA in macrophages w as correlated with secretion of IL-6 and TNF-alpha in cell supernatant . The release of IL-6 was HGP92 concentration dependent over a range o f 0.3-10 mu g/ml with a maximum production obtained after a 24 h incub ation of inflammatory macrophages with HGP92. This effect was shown no t to be due to contamination of HGP92 by LPS since inflammatory macrop hages from C57BL/6 mice were responsive to HGP92 pretreated with polym yxin B sulfate and unresponsive to heated HGP92, Stimulating activity of HGP92 was confirmed using macrophages from C3H/HeJ mice, These resu lts suggest that HGP92 might modulate the immune responses by increasi ng cytokine production by macrophages.