Interleukin-10 enhances resolution of pulmonary inflammation in
vivo by promoting apoptosis of neutrophils.
Cox, Gerard.
Department of Medicine, McMaster University, 1200 Main St. West,
Hamilton, Ontario L8N 3Z5
APStracts 3:0087L, 1996.
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. Since IL-10 can act on other cells to regulate
inflammatory events, and 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[mu]g of IL-10 with LPS, 6 [mu]g 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.
Received 14 March 1996; accepted in final form 17 May 1996.
APS Manuscript Number L83-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96