Dual mechanisms of far fever induction inside and outside the blood-brain barrier in rabbits.

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Intravenous bacterial endotoxin, or endogenous pyrogen, in high concentration both caused biphasic fever in rabbits. In low concentration they produced only monophasic fever. Human recombinant interleukin 1 also caused the same pattern of febrile response, dependig on their doses administered, to those with bacterial endotoxin or endogenous pyrogen.<BR>Subcutaneous indomethacin suppressed the first phase of fever produced by high concentraion of intravenous endotoxin or endogenous pyrogen, but not the second phase. Intracerebroventricular injection of indomethacin reduced only the second phase of fever produced by high concentration of intravenous endotoxin or endogenous pyrogen, but not the first phase. Intraventricular injection of endotoxin or endogenous pyrogen caused slow monotonic fever. This was suppressed by intraventricular, but no by subcutaneous, indomethacin.<BR>Hence, it is concluded that the first phase of biphasic fever is caused by pyrogen acting via structures outside the blood-brain barrier and the second phase by pyrogen acting via structures within the blood-brain barrier.
日本炎症・再生医学会の論文