title: Hemorrhage suppresses fever, interleukin-6, and tumor necrosis factor-alpha responses to lipopolysaccharide in rats.
abstract: The purpose of this study was to test the hypothesis that attenuation of the fever response to lipopolysaccharide (LPS) following hemorrhage is accompanied by changes in serum glucocorticoid levels and a decreased bioactivity of TNF-alpha and IL-6 in plasma. Hemorrhage was induced in rats by the withdrawal of 20% of estimated total blood volume. LPS (50 microg/kg) or saline were injected intraperitoneally immediately after the hemorrhage. Blood samples were taken 1.5 h for TNF-alpha bioactivity and corticosterone measurements and 5 h after treatment for IL-6 bioactivity. Body temperature (Tb) was measured by biotelemetry. The 20% hemorrhage led to a significant reduction in hematocrit measured at 1.5 and 5 h after treatment. Furthermore, 20% hemorrhage caused a substantial elevation in serum corticosterone measured by radioimmunoassay at 1.5 h after treatment. This high concentration of corticosterone was not further potentiated by injection of LPS. Hemorrhaged rats treated with LPS responded with a markedly attenuated fever. Both TNF-alpha and IL-6 rises in the circulation due to LPS injection were significantly smaller in hemorrhaged rats compared to nonhemorrhaged LPS-injected rats. However, this degree of hemorrhage did not alter the T(b) or plasma TNF-alpha and IL-6 activity in hemorrhaged rats injected with saline. These results show that the inhibitory effect of hemorrhage on LPS-induced fever may be related to the decreased TNF-alpha and IL-6 activity in plasma. Hemorrhage-induced high level of corticosterone might contribute to the attenuation of fever, perhaps via the suppression of pyrogenic cytokines.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, N. Mex., USA. daryk@lucy.tli.org
authors.forename: D
authors.initials: D
authors.lastname: Soszynski
authors.forename: W
authors.initials: W
authors.lastname: Kozak
authors.forename: K
authors.initials: K
authors.lastname: Rudolph
authors.forename: L R
authors.initials: LR
authors.lastname: Leon
authors.forename: C A
authors.initials: CA
authors.lastname: Conn
authors.forename: M J
authors.initials: MJ
authors.lastname: Kluger
mesh_terms: D000818:Animals; D005334:Fever / Q000378:metabolism / Q000503:physiopathology*; D006470:Hemorrhage / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha