Macrophage deactivation by interleukin 10.

TLDR

IL‑10 can modulate macrophage activity, potentially suppressing lymphocyte function at low doses and impairing antimicrobial and tumoricidal responses at higher doses, and its effects differ from those of TGF‑β and macrophage deactivation factor. Recombinant IL‑10 potently suppresses TNF‑α release from macrophages (IC50 ≈ 0.04 U/ml) and strongly inhibits reactive oxygen intermediate production (IC50 ≈ 3.7 U/ml) while only weakly affecting reactive nitrogen intermediates, and neutralizing antibody studies show these suppressor factors act independently.

Abstract

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 microgram/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.