Corticosteroid and Antihistamine Modification of Bleomycin-lnduced Fever 1

Abstract

Summary

Fever is a common and frequently debilitating complication following the administration of bleomycin to patients. Bleomycin-induced fever has been demonstrated in rabbits where it is dose related and mediated through the release of endogenous pyrogen from phagocytes. Because cortico-steroids are known to suppress fever in several clinical states and to reduce endogenous pyrogen release from stimulated human phagocytes in vitro the effect of hydrocorti-sone pretreatment on bleomycin-induced fever was studied. All rabbits studied received bleomycin 1 unit/kg i.v. One group received no other medication. A second group received hydrocortisone 5 mg/kg i.v. 1 hr before bleomycin, and a third group received the same dose of hydrocortisone administered as a single injection 1 hr after bleomycin. Hydrocor-tisone-pretreated rabbits, 44%, developed bleomycin-induced fever compared to 90% of the rabbits who received bleomycin alone. Hydrocortisone pretreatment diminished the mean peak fever (ΔT) from 0.80° to 0.39° and prolonged the latent period from 2.79 to 3.81 hr. Hydrocortisone administered 1 hr after bleomycin diminished the mean Δ T but had only slight effect on the incidence of fever and no effect on the latency. These studies provide rationale for clinical use of single-dose corticosteroid pretreatment in patients with bleomycin-induced fever. Anti-histamine pretreatment with the H₁ receptor antagonist diphenhydramine was ineffective in protecting rabbits from bleomycin-induced fever; however, a species-specific effect might explain this result.