In vitro tumor necrosis factor induction assay for analysis of febrile toxicity associated with amphotericin B preparations.

Amphotericin B can stimulate macrophages to produce tumor necrosis factor alpha (TNF alpha), one of the inflammatory mediators that may be responsible for the febrile toxicity associated with drug administration. The purpose of this study was to compare the in vitro TNF-inducing activity of one recalled lot of an amphotericin B preparation which was associated with more frequent febrile reactions in patients with a preparation not associated with a greater incidence of febrile reaction. We found that the former preparation induced significantly more TNF than the latter preparation, and the in vitro data correlated with the results of rabbit pyrogen testing. The in vitro TNF induction assay may serve as a screening tool for the selection of the least pyrogenic lots of amphotericin B preparation.