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Department of Internal Medicine and the John B. Pierce Foundation Laboratory, Yale University School of Medicine, New Haven, Connecticut, U.S.A.

1. A method was devised to sample cerebrospinal fluid (c.s.f.) from the third ventricle of conscious rabbits.

2. Levels of PGE were measured in c.s.f. withdrawn from the third ventricle of rabbits exposed to a variety of manipulations of both brain and body core temperatures which mimicked various facets of fever in these animals. These results were compared to the levels of PGE in the c.s.f. of the same rabbits made febrile by I.V. injections of endogenous pyrogen.

3. Levels of PGE in ventricular c.s.f. remained unaltered at 2-3 ng/ml. during exposure to cold, hyperthermia due to heat exposure, hypothalamic cooling or hypothalamic heating, whereas during fever produced by endogenous pyrogen, they rose to an average of 11-12 ng/ml. Furthermore, a significant positive correlation was established between the level of PGE measured in the c.s.f. and the subsequent height of the fever produced by the pyrogen.

4. Since production of PGE within the brain is not caused by changes in the brain or body temperatures which are comparable to those observed during fever, and yet greater than fivefold increases in the PGE levels in c.s.f. are produced by I.V. injections of endogenous pyrogen, it is concluded that PGE production in the brain is involved in the pathogenesis of fever.

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