Corticosteroid and Antihistamine Modification of Bleomycin-lnduced Fever

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Abstract
Fever is a common and frequently debilitating complication following the administration of bleomycin to cancer patients. Bleomycin-induced fever was demonstrated in rabbits where it is dose related and mediated through the release of endogenous pyrogen from phagocytes. Because corticosteroids suppress fever in several clinical states and reduce endogenous pyrogen release from stimulated human phagocytes in vitro, the effect of hydrocortisone pretreatment on bleomycin-induced fever was studied. All rabbits studied received bleomycin 1 unit/kg i.v. One group received no other medication. A 2nd group received hydrocortisone 5 mg/kg i.v. 1 h before bleomycin, and a 3rd group received the same dose of hydrocortisone administered as a single injection 1 h after bleomycin. Of the hydrocortisone-pretreated rabbits, 44% developed bleomycin-induced fever compared to 90% of the rabbits who received bleomycin alone. Hydrocortisone pretreatment diminished the mean peak fever (.delta.T) from 0.80.degree. to 0.39.degree. and prolonged the latent period from 2.79 to 3.81 h. Hydrocortisone administered 1 h after bleomycin diminished the mean .delta.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. Antihistamine pretreatment with the H1 receptor antagonist diphenhydramine was ineffective in protecting rabbits from bleomycin-induced fever; a species-specific effect might explain this result.

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