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

Abstract

The authors investigated the ability of interleukin-10 (IL-10) to modulate some constitutive or interferon-gamma (IFN-gamma)-enhanced activities of human neutrophils. An 18h culture of neutrophils with IL-10 dose-dependently down-regulated their capacity to produce O(2)- 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 Fc gamma RI, Fc gamma RII, Fc gamma RIII, CR1, CR3 and Fc gamma R- and CR-mediated phagocytosis were not modified by the cytokine. Culture of neutrophils with IFN-gamma (100 U/ml) did not modify their Fc gamma R- and CR-mediated phagocytosis, but significantly up-regulated Fc gamma RI and CR3 membrane expression as well as their oxidative metabolism and antibody-dependent cellular cytotoxicity (ADCC). When IL-10 and IFN-gamma were added simultaneously to neutrophil culture, IL-10 dose-dependently reduced IFN-gamma-induced increase of CR3 expression, O(2)- production (in response to both FMLP and phorbol 12-myristate 13-acetate, or PMA) and ADCC, but did not change Fc gamma RI 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.