Organ interactions in sepsis. Host defense and the hepatic-pulmonary macrophage axis
M. P. Callery, T. Kamei, M. J. Mangino and M. W. Flye
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.
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.
