Interleukin-10 Down-Regulates Oxidative Metabolism and Antibody-Dependent Cellular Cytotoxicity of Human Neutrophils

The authors investigated the ability of interleukin-10 (IL-10) to modulate some constitutive or interferon-γ (IFN-γ)-enhanced activities of human neutrophils. An 18 h culture of neutrophils with IL-10 dose-dependently down-regulated their capacity to produce O₂⁻ and lucigenin-amplified chemiluminescence in response to n-formyl-methionyl-leucylphenyl-alanine (FMLP). Furthermore, treatment of neutrophils with IL-10 decreased in a dose-dependent fashion, their capacity to lyse antibody-coated sheep erythrocytes. Membrane expression of FcγRI, FcγRII, FcγRIII, CR1, CR3 and FcγR- and CR-mediated phagocytosis were not modified by the cytokine. Culture of neutrophils with IFN-γ (100 U/ml) did not modify their FcγR- and CR-mediated phagocytosis, but significantly up-regulated FcγRI and CR3 membrane expression as well as their oxidative metabolism and antibody-dependent cellular cytotoxicity (ADCC). When IL-10 and IFN-γ were added simultaneously to neutrophil culture, IL-10 dose-dependently reduced IFN-γ-induced increase of CR3 expression, O₂⁻ production (in response to both FMLP and phorbol 12-myristate 13-acetate, or PMA) and ADCC, but did not change FcγRI expression on phagocytes. These results demonstrate that IL-10 is a significant neutrophil deactivator and provide new information on the role of IL-10 in the regulation of neutrophil-mediated inflammatory processes.