The Kupffer cell protects against acute lung injury in a rat peritonitis model: role of IL-10

Abstract

The possibility that Kupffer cells (KCs) play key beneficial and deleterious roles in multiple organ injury in sepsis has been discussed. The role of KCs in lung injury in a rat peritonitis model was investigated. Specifically, the involvement of interleukin (IL)-10, which has anti-inflammatory effects, was examined. Rats were given saline or gadolinium chloride (GdCl3), a KC toxicant, 24 h before cecal ligation and puncture (CLP). Survival was assessed for 7 days after CLP. The liver, lung, and serum were harvested, and the expression of cytokines was assessed. Macrophages were isolated from each organ after CLP, and the mRNA expression of inflammatory mediators was assessed. GdCl3 treatment increased lung injury and mortality. Plasma endotoxin levels were significantly greater, whereas serum IL-10 levels were lower in the GdCl3 than in the control group after CLP. IL-10 levels were significantly greater in the aorta than the hepatic vein. The mRNA expression of IL-10 was less in KCs from the GdCl3 than the control group. In the liver, the expression of IL-10 increased rapidly and continuously, up to 9 h in the control group, but values were significantly lower in the GdCl3 group. Rabbit anti-rat IL-10 antibodies were injected just after CLP to investigate the effects of immunoneutralization of endogenously produced IL-10. In the antibody-treated group, lung injury and mortality increased compared with animals treated with rabbit immunoglobulin G. Taken together, these results indicate that KCs play a protective role in lung injury in sepsis by production of IL-10.

Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits withPseudomonas aeruginosapneumonia

“…5B). These findings support and extend the work of Emmanuilidis et al (16) and Kono et al (34). In addition, Data are shown as means Ϯ SE.…”

Mannose prevents lipopolysaccharide-induced acute lung injury in rats

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Growth Factors and Cytokines in Acute Lung Injury

“…Induction of sepsis (either due to endotoxin administration or CLP) results in the systemic production of IL-10, and blockade of IL-10 during the septic response dramatically enhances sepsis-induced inflammatory cytokine release, tissue injury, and mortality (52,118,223,232). Similarly, IL-10 −/− mice have prolonged inflammation and enhanced lung injury following intrapulmonary challenge with cytotoxic strains of P. aeruginosa, intratracheal LPS administration, or acute pancreatitis (80,217).…”

“…IL-10 is produced by a variety of cell types, including macrophages, dendritic cells, NK cells, and T cells, especially regulatory T cells (T reg ) (56,118). Nonmyeloid cell populations also express IL-10, including epithelial cells and tumor cells.…”