Alveolar macrophage deactivation in murine septic peritonitis: Role of interleukin 10

Sepsis predisposes the host to a number of infectious sequelae, particularl y the development of nosocomial pneumonia. Mechanisms by which sepsis resul ts in impairment of lung antibacterial host defense have not been well defi ned. Alveolar macrophages (AM) represent important immune effector cells of the lung airspace. In this study, we examined the effects of cecal ligatio n and puncture (CLP) on murine AM function ex vivo, including the expressio n of proinflammatory cytokines and AM phagocytic activity. AM were harveste d from mice subjected to a sham operation and CLP 24 h after laparotomy, ad herence purified, and challenged with lipopolysaccharide (LPS) or left unst imulated. Both unstimulated and LPS-stimulated AM from mice subjected to CL P (CLP mice) produced significantly smaller amounts of proinflammatory cyto kines tumor necrosis factor alpha and interleukin (IL-12) and C-X-C chemoki nes KC and macrophage inflammatory protein 2 than similarly treated AM from animals subjected to a sham operation. Furthermore, AM isolated from CLP m ice 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 i n plasma and peritoneal fluid. Interestingly, the impairment in AM proinfla mmatory-cytokine production and phagocytic activity observed in AM from CLP mice was partially reversed by the in vivo neutralization of IL-10 prior t o AM harvest. These observations suggest that abdominal sepsis syndrome res ults in significant impairment in AM effector cell function, which is media ted, in part, by sepsis-induced expression of IL-10.