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 is dependent upon the coordinated expression of both pro- and anti-inflammatory cytokines. Interleukin-10 (IL-10) is a recently described cytokine with potent anti-inflammatory properties in vivo and in vitro. In this study we investigated whether IL-10 could directly regulate the ability of neutrophils (PMN) to phagocytose and kill bacteria. Initial studies demonstrated that human recombinant IL-10 (hrIL-10) inhibited the ability of PMN to phagocytose Escherichia coli in vitro. Inhibition of phagocytosis occurred in the absence of changes in CR1 (C3b) or Fc receptor expression, as treatment of PMN with IL-10 failed to induce significant changes in Fc gamma IIR, Fc gamma IIIR or CR1 cell surface expression. However, incubation of PMN with IL-10 resulted in a dose-dependent decrease in CDIIb (Mac-1) expression. In addition to effects on PMN phagocytosis, hrIL-10 significantly attenuated PMN microbicidal activity, as bactericidal assays revealed that co-incubation of PMN with hrIL-10 resulted in a marked decrease in killing of phagocytosed bacteria. Furthermore, IL-10 inhibited the production of superoxide from PMA-stimulated PMN, suggesting that the detrimental effects of IL-10 on PMN microbicidal activity were due, in part, to suppression of respiratory burst. In summary, our studies indicate that IL-10 inhibits PMN-dependent phagocytosis and killing of E. coli in vitro, and suggest that this cytokine may impair effective antibacterial host defense in vivo.
Department of Medicine, University of Michigan Medical School, Ann Arbor 48109-0360, USA.
L L
LL
Laichalk
J M
JM
Danforth
T J
TJ
Standiford
D003179:Complement C3b / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000502:physiology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D017463:Receptors, Complement 3b / Q000096:biosynthesis; D011961:Receptors, Fc / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D016177:Macrophage-1 Antigen; D011956:Receptors, Cell Surface; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D011994:Recombinant Proteins; D013481:Superoxides; D016753:Interleukin-10; D003179:Complement C3b