Macrophage Deactivation by Interleukln 10

Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (mOb) to release tumor necrosis factor a (TNF-o~). The ICs0 of IL-10 for the suppression of TNF-ol release induced by 0.5 #g/ml lipopolysaccharide was 0.04 _+ 0.03 U/ml, with as little as 1 U/ml suppressing TNF-ot production by a factor of 21.4 + 2.5. At 10 U/ml, II.-10 markedly suppressed mOb release of reactive oxygen intermediates (ROI) (ICso 3.7 _+ 1.8 U/ml), but only weakly inhibited mOb release of reactive nitrogen intermediates (RNI). Since TNF-a is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that mOb exposed to low concentrations of IL-10 suppress lymphocytes, mOb deactivated by higher concentrations of IL.10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-ot, ROI, and RNI are major antimicrobial and tumoricidal products of mob. Ibl0's effects on mOb overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse mOb, transforming growth factor fl and macrophage deactivation factor. Based on results with neutralizing antibodies, all three mOb suppressor factors appear to act independently.