MACROPHAGE DEACTIVATION BY INTERLEUKIN-10

Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m-phi) to release tumor necrosis factor-alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5-mu-g/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m-phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m-phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m-phi exposed to low concentrations of IL-10 suppress lymphocytes. M-phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m-phi. IL-10's effects on m-phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m-phi, transforming growth factor-beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m-phi suppressor factors appear to act independently.