Hemorrhage suppresses fever, interleukin-6, and tumor necrosis factor-alpha responses to lipopolysaccharide in rats.
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.
Soszynski
D
D
Lovelace Respiratory Research Institute, Albuquerque, N. Mex., USA. daryk@lucy.tli.org
Kozak
W
W
Rudolph
K
K
Leon
L R
LR
Conn
C A
CA
Kluger
M J
MJ
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*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha