IL-10 enhances resolution of pulmonary inflammation in vivo by promoting apoptosis of neutrophils.
Interleukin-10 (IL-10) has been shown to be protective in models of sepsis. This protection is mediated in part by inhibition of monokine-dependent processes. Because IL-10 can act on other cells to regulate inflammatory events, and because we have previously shown that clearance of inflammation is an active process, we examined whether IL-10 could regulate processes of resolution during pulmonary inflammation induced by lipopolysaccharide (LPS) challenge. Administration of 1 microgram of IL-10 with 6 micrograms LPS intratracheally to rats did not alter the time of onset or the magnitude of the initial response, as assessed by bronchoalveolar lavage (BAL) neutrophilia. However, the extent of the neutrophilia was markedly reduced at 18 h, and longer, after challenge. During ex vivo culture of cells obtained by BAL, neutrophils died by apoptosis and were engulfed by macrophages. Clearance of neutrophils was more rapid in the cultured BAL of rats treated with IL-10. In separate experiments, IL-10 did not reduce survival rates of untreated human neutrophils, but did inhibit LPS-induced increases in survival in a dose-dependent fashion. Thus IL-10 did not modulate the onset of, or peak of, neutrophil accumulation in response to LPS but did promote the clearance of recruited neutrophils in vivo. The mechanism of this anti-inflammatory action may be through the prevention of stimulated increases in neutrophil survival.
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
G
G
Cox
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10