Intraventricular injections of drugs which inhibit phospholipase A2 suppress fever in rabbits.

Injection of two chemically dissimilar inhibitors of phospholipase A2 (mepacrine and parabromophenacylbromide) into the cerebral ventricles of rabbits inhibited the febrile response to endogenous pyrogen given by the same route. 2. The same doses of the inhibitors given intravenously did not affect the febrile response to endogenous pyrogen given into the ventricles, indicating that their action was central. 3. When given intraventricularly the inhibitors did not affect the maintenance of core temperature in a cold environment, indicating that they did not impair thermoregulatory ability. 4. The inhibitors had no effect on the temperature rise following intraventricular injection of arachidonic acid. 5. These observations are compatible with the proposition that one or more metabolic products of arachidonic acid other than prostaglandin are involved in pyrogenesis.