INTERLEUKIN-10 INHIBITS NEUTROPHIL PHAGOCYTIC AND BACTERICIDAL ACTIVITY

Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells, which i s dependent upon the coordinated expression of both pro- and anti-infl ammatory cytokines. Interleukin-10 (IL-10) is a recently described cyt okine with potent anti-inflammatory properties in vivo and in vitro. I n this study we investigated whether IL-10 could directly regulate the ability of neutrophils (PMN) to phagocytose and kill bacteria. Initia l studies demonstrated that human recombinant IL-10 (hrIL-10) inhibite d the ability of PMN to phagocytose Escherichia coli in vitro. Inhibit ion of phagocytosis occurred in the absence of changes in CRI (C3b) or Fc receptor expression, as treatment of PMN with IL-10 failed to indu ce significant changes in Fc gamma IIR, Fc gamma IIIR or CR1 cell surf ace expression. However, incubation of PMN with IL-10 resulted in a do se-dependent decrease in CD11b (Mac-1) expression. In addition to effe cts on PMN phagocytosis, hrIL-10 significantly attenuated PMN microbic idal activity, as bactericidal assays revealed that co-incubation of P MN with hrIL-10 resulted in a marked decrease in killing of phagocytos ed bacteria. Furthermore, IL-10 inhibited the production of superoxide from PMA-stimulated PMN, suggesting that the detrimental effects of I L-10 on PMN microbicidal activity were due, in part, to suppression of respiratory burst. In summary, our studies indicate that IL-10 inhibi ts PMN-dependent phagocytosis and killing of E. coli in vitro, and sug gest that this cytokine may impair effective antibacterial host defens e in vivo.