Alveolar macrophage deactivation in murine septic peritonitis: role of interleukin 10.
Sepsis predisposes the host to a number of infectious sequelae, particularly the development of nosocomial pneumonia. Mechanisms by which sepsis results in impairment of lung antibacterial host defense have not been well defined. Alveolar macrophages (AM) represent important immune effector cells of the lung airspace. In this study, we examined the effects of cecal ligation and puncture (CLP) on murine AM function ex vivo, including the expression of proinflammatory cytokines and AM phagocytic activity. AM were harvested from mice subjected to a sham operation and CLP 24 h after laparotomy, adherence purified, and challenged with lipopolysaccharide (LPS) or left unstimulated. Both unstimulated and LPS-stimulated AM from mice subjected to CLP (CLP mice) produced significantly smaller amounts of proinflammatory cytokines tumor necrosis factor alpha and interleukin (IL-12) and C-X-C chemokines KC and macrophage inflammatory protein 2 than similarly treated AM from animals subjected to a sham operation. Furthermore, AM isolated from CLP mice displayed a marked impairment in phagocytic activity, as determined by flow cytometry, with this defect persisting to 48 h post-CLP. Induction of peritoneal sepsis syndrome resulted in a time-dependent increase in IL-10 in plasma and peritoneal fluid. Interestingly, the impairment in AM proinflammatory-cytokine production and phagocytic activity observed in AM from CLP mice was partially reversed by the in vivo neutralization of IL-10 prior to AM harvest. These observations suggest that abdominal sepsis syndrome results in significant impairment in AM effector cell function, which is mediated, in part, by sepsis-induced expression of IL-10.
Reddy
R C
RC
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The University of Michigan Medical School, Ann Arbor, Michigan 48109-0360, USA.
Chen
G H
GH
Newstead
M W
MW
Moore
T
T
Zeng
X
X
Tateda
K
K
Standiford
T J
TJ
D000818:Animals; D017209:Apoptosis; D001202:Ascitic Fluid / Q000276:immunology; D001769:Blood / Q000276:immunology; D002432:Cecum / Q000601:surgery; D005260:Female; D016753:Interleukin-10 / Q000276:immunology*; D008026:Ligation; D016676:Macrophages, Alveolar / Q000276:immunology*; D051379:Mice; D009500:Neutralization Tests; D010538:Peritonitis / Q000276:immunology*; D010587:Phagocytosis; D011677:Punctures; D018805:Sepsis / Q000276:immunology*
D016753:Interleukin-10