Pulmonary cytokine and chemokine mRNA levels after inhalation of lipopolysaccharide in C57BL/6 mice

Inhaled endotoxin (lipopolysaccharide, LPS) can induce acute lung injury an d at high doses may lead to respiratory distress syndrome. Using a mouse mo del of acute lung inflammation induced by inhalation of low doses of LPS we examined the kinetics of chemokine, proinflammatory cytokine, and metallot hionein. Eight-week-old C57BL/6 mice were dosed for 10 min with LPS, result ing in an estimated alveolar dose of <10 ng LPS/mouse, and euthanized 2, 6, or 24 h postexposure. Analysis of bronchoalveolar lavage fluid demonstrate d increased polymorphonuclear neutrophils (PMNs) of 6.94, 32.7, and 38.8% a fter 2, 6, and 24 h, respectively Examination of proinflammatory cytokine, chemokine, and Mt mRNA in the lung revealed increases for messages encoding IL-1 alpha, IL-1 beta, IL-6, IFN-gamma, TNF alpha, Eotaxin, MIP-1 alpha, M IP-1 beta, MIP-2, Mt, and IP-10, while messages encoding IL-12, IL-10, IFN- beta, Ltn, MCP-1, TGFP(1+2), and RANTES were unchanged from those of sham-e xposed mice 2 h postexposure. By 6 h most messages had returned to near con trol levels. Comparison to 5 mg/kg body weight intraperitoneal injection an d 5 mu g/mouse intratracheal instillation 2 h postexposure demonstrated sim ilar message responses. Our results demonstrate that low levels of LPS expo sure by inhalation induce a strong PMN response and a selective cytokine re sponse in the lung, supporting the hypothesis that PMNs may regulate inflam matory processes via cytokine and chemokine response. (C) 1998 Society of T oxicology.