Intracerebroventricular and preoptic injections of leukotrienes C4, D4, and E4 in the rat: lack of febrile effect.

Experiments were performed to ascertain the effect on core temperature in the rat of central administration of 3 products of the lipoxygenase pathway of arachidonate metabolism. The agents tested were leukotrienes C4, D4, and E4 (LTC4, LTD4, LTE4). In one series of rats, the leukotrienes were injected into the ventral aspect of the third cerebral ventricle (5 microliter injection volume). Each rat received, in separate experimental sessions, an injection of a control solution, of 1 microgram of prostaglandin E1 (PGE1) and of 1 microgram of LTC4, LTD4, or LTE4. In another series of rats, bilateral 1 microliter injections into the tissue of the preoptic region were made. Each animal received a control solution, 40 ng PGE1 (20 ng/side) and 400 ng LTC4, LTD4, or LTE4 (200 ng/side). Neither the intraventricular nor the preoptic injections of any of the leukotrienes produced a significant increase in colonic temperature. However, PGE1 injected intraventricularly or into the preoptic region produced a large, rapidly developing core temperature rise. The strong febrile response to PGE1 and the results of dye distribution studies indicate that the lack of effect of the leukotrienes was not due to incorrect injection cannula placement. The ineffectiveness of the leukotrienes also cannot be attributed to loss of biological activity of these agents during storage. Near the end of the study, samples of each leukotriene were assayed using the guinea pig tracheal strip method and were found to be highly active. The results suggest that, at least in the rat, these 3 arachidonate metabolites are not likely to be important mediators of fever.