title: Inhibition of the Kupffer cell and neutralization of IL-10 increase the expression of chemokines in the lung in a rat peritonitis model.
abstract: BACKGROUND
  Elimination of Kupffer cells (KCs) exacerbated acute lung injury and mortality by inhibiting serum interleukin (IL)-10 levels in a rat peritonitis model. Since infiltrating inflammatory cells play a pivotal role in organ injury, the specific purpose of this study was to determine whether elimination of the KC and systemic IL-10 affect the expression of inflammatory mediators and the number of infiltrating inflammatory cells in the lung in the peritonitis model.
  
  
  METHODS
  Rats were given saline or gadolinium chloride (GdCl(3)), a KC toxicant, 24 h before cecal ligation and puncture (CLP). Tissue and serum samples were harvested after CLP, and the expression of inflammatory mediators was investigated. In another set of experiments, anti-rat IL-10 antibodies (anti-IL-10 Abs) were injected immediately after CLP to investigate the effects of immunoneutralization of endogenous IL-10.
  
  
  RESULTS
  Serum levels of proinflammatory cytokines and chemokines were significantly greater in the GdCl(3) group than the control group after CLP. Furthermore, expression inflammatory mediators, as well as the number of infiltrating inflammatory cells in the lung were significantly greater in the GdCl(3) group than the control group. Alternatively, serum levels of inflammatory cytokines and chemokines, and the number of infiltrating inflammatory cells into the lung also increased significantly in rats treated with anti-IL-10 Abs compared with IgG after CLP.
  
  
  CONCLUSIONS
  Thus, depletion of KCs and neutralization of IL-10 increased the expression of chemokines and the number of infiltrating inflammatory cells in the lung, leading to exacerbated acute lung injury in sepsis.
authors.affiliation: First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. hkouno@yamanashi.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kono
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Masato
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: Yu
authors.initials: Y
authors.lastname: Hirai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishii
authors.forename: Naohiro
authors.initials: N
authors.lastname: Hosomura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka