Organ interactions in sepsis. Host defense and the hepatic-pulmonary macrophage axis.
Endotoxin (lipopolysaccharide [LPS]) and tumor necrosis factor (TNF-alpha) 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-alpha, 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-alpha levels peaked early before decreasing as regulatory prostaglandin E2 levels rose. In contrast, AM TNF-alpha 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-alpha production within the pulmonary microenvironment.
Callery
M P
MP
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.
Kamei
T
T
Mangino
M J
MJ
Flye
M W
MW
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004926:Escherichia coli; D005260:Female; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D011920:Rats, Inbred WF; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone