• Endotoxin (lipopolysaccharide [LPS]) and tumor necrosis factor (TNF-α) have been implicated in the pathogenesis of sepsis-induced adult respiratory distress syndrome. To evaluate the possible interaction of the hepatic-pulmonary macrophage axis in the adult respiratory distress syndrome, we compared the kinetics of immunosuppressive prostaglandin E2, TNF-α, and interleukin 6 production in LPS-stimulated Kupffer cells and alveolar macrophages (AMs). Interleukin 6 production by Kupffer cells was significantly higher than for equal numbers of AMs. Kupffer cell TNF-α levels peaked early before decreasing as regulatory prostaglandin E2 levels rose. In contrast, AM TNF-α levels rose sharply and remained significantly higher than for Kupffer cells throughout culture coincident with negligible prostaglandin E2 production. Kupffer cell sequestration of LPS may normally invoke a coordinated cytokine response able to locally induce acute-phase hepatocytes. In hepatic failure, however, LPS spillover to the lung may promote adult respiratory distress syndrome by inducing unregulated AM TNF-α production within the pulmonary microenvironment.
(Arch Surg. 1991;126:28-32)
Callery MP, Kamei T, Mangino MJ, Flye MW. Organ Interactions in Sepsis: Host Defense and the Hepatic-Pulmonary Macrophage Axis. Arch Surg. 1991;126(1):28–32. doi:10.1001/archsurg.1991.01410250032004
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