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In vitro tumor necrosis factor induction assay for analysis of febrile toxicity associated with amphotericin B
1Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20892.
Abstract:
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.
Insights
Amphotericin B can cause fever by stimulating tumor necrosis factor alpha (TNF-alpha). This study found a recalled Amphotericin B lot induced more TNF-alpha in vitro, correlating with patient reactions and pyrogen tests.
Area of Science:
- Immunology
- Pharmacology
- Toxicology
Background:
- Amphotericin B administration is linked to febrile toxicity.
- Tumor necrosis factor alpha (TNF-alpha) is an inflammatory mediator implicated in Amphotericin B-induced fever.
- Variations in drug lots may influence patient reactions.
Purpose of the Study:
- To compare the in vitro TNF-alpha-inducing activity of two Amphotericin B lots.
- To determine if in vitro TNF-alpha induction correlates with clinical febrile reactions.
- To evaluate the utility of an in vitro assay for predicting pyrogenicity.
Main Methods:
- In vitro testing of Amphotericin B preparations for TNF-alpha induction by macrophages.
- Comparison of TNF-alpha levels between a recalled lot and a non-recalled lot.
- Correlation analysis with rabbit pyrogen testing results.
Main Results:
- The recalled Amphotericin B lot demonstrated significantly higher in vitro TNF-alpha induction compared to the non-recalled lot.
- In vitro TNF-alpha induction levels correlated with results from rabbit pyrogen testing.
- The findings suggest a link between TNF-alpha production and Amphotericin B pyrogenicity.
Conclusions:
- In vitro TNF-alpha induction assay can identify Amphotericin B lots with higher pyrogenic potential.
- This assay may serve as a valuable screening tool to select less pyrogenic drug preparations.
- Reducing pyrogenic reactions can improve patient tolerance to Amphotericin B therapy.
