Effect of IL-10 on neutrophil recruitment and survival after Pseudomonas aeruginosa challenge

Lei Sun, Ren Feng Guo, Michael W. Newstead, Theodore J. Standiford, Demetrio R. Macariola, Thomas P. Shanley

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

IL-10 is a potent, endogenous anti-inflammatory cytokine known to decrease cytokine and keratinocyte-derived chemokine (KC) expression. Traditionally, in vivo effects of IL-10 were extrapolated fromstudiesemployingsystemic antibodyneutralization.As aresult, divergent data regarding the protective and/or harmful roles of IL-10 have been reported. In this study, we used a lung-specific, tetracycline-inducible IL-10 overexpression-transgenic (IL-10 OE) mouse to study the effects of IL-10 overexpression on Pseudomonas aeruginosa-induced lung inflammation and corresponding survival in mice. Overexpression of IL-10 in the lung significantly increased mortality. During the early phase after infection (6-hours after infection), neutrophil recruitment as well as cytokine (TNF-α) and chemokine (KC) expression were significantly decreased in the IL-10 OE mice, which resulted in attenuated bacterial clearance. In contrast, overzealous production of KC and TNF-α intensified neutrophil infiltration and increased vascular leakage in IL-10 OE mice at the later stage of infection (24 hours after infection). Neutrophil depletion showed impaired bacterial clearance in both control and IL-10 OE mice, and further enhanced mouse mortality, whereas exogenous administration of KC reversed this finding. Our data indicate that early neutrophil recruitment is important for combating bacterial infection, and that the inhibition of neutrophil recruitment by IL-10 results in insufficient bacteria clearance in the lung, leading to excessive development of inflammation and increased mortality.

Original languageEnglish (US)
Pages (from-to)76-84
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume41
Issue number1
DOIs
StatePublished - Jul 1 2009

Keywords

  • Chemokines
  • IL-10
  • Neutrophils
  • Pseudomonas

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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