Hypothermia to endotoxin involves reduced thermogenesis, macrophage-dependent mechanisms, and prostaglandins.
At a subthermoneutral ambient temperature of 24 degrees C, intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats resulted in hypothermia associated with a fall in oxygen consumption followed by fever. At the thermoneutral ambient temperature of 30 degrees C, animals only responded to LPS with fever. The hypothermia and reduction in oxygen consumption were attenuated in rats with eliminated peripheral macrophages. By contrast, macrophage elimination did not affect the febrile response to LPS. Both the hypothermia and the febrile response to LPS were prevented by peripheral administration of the cyclooxygenase inhibitor indomethacin. We conclude that hypothermia in response to LPS is caused by reduced thermogenesis, involves antipyretic products released from peripheral macrophages, and is mediated by prostaglandins. In addition, the febrile response likewise involves prostaglandins, but in contrast to the hypothermia appears to be independent of pyrogens released from peripheral macrophages. Previously, we reported the induction of the pyrogen interleukin-1 in the brain during the time course of the febrile response to LPS (34). The latter observations support the hypothesis that the second phase of biphasic fever is mediated by synthesis and action of pyrogens inside the blood-brain barrier.
Derijk
R H
RH
Department of Pharmacology, Free University, Amsterdam, The Netherlands.
Van Kampen
M
M
Van Rooijen
N
N
Berkenbosch
F
F
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation; D003106:Colon / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D004926:Escherichia coli; D007035:Hypothermia / Q000139:chemically induced* / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D010101:Oxygen Consumption; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration; D013696:Temperature
D004731:Endotoxins; D011453:Prostaglandins; D007213:Indomethacin