Induction of Prostaglandin Synthesis as the Mechanism Responsible for the Chills and Fever Produced by Infusing Amphotericin B

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Abstract
Amphotericin B produces chills and fever in a significant proportion of patients who receive this drug. The mechanism for this adverse effect is unknown. Amphotericin B suspension at a concentration of 1.0 µg/ml was demonstrated to be a potent inducer of prostaglandin E2 synthesis by human and murine mononuclear cells in vitro. A doubleblind, placebo-controlled clinical trial demonstrated that ibuprofen (10 mg/kg), a potent inhibitor of prostaglandin synthesis, administered 30 min before amphotericin B administration reduced the incidence of chilling from 87% to 49% (P = .01); the incidence of chilling reactions considered severe was reduced from 69% to 15% (P = .008). Wepostulate that the chills and fever produced by an infusion of amphotericin B are mediated through prostaglandin E2 synthesis. Ibuprofen is therapeutically useful in ameliorating the chills and fever caused by amphotericin B.