Comparison of ketoconazole and amphotericin B in interference with thymidine uptake by and blastogenesis of lymphocytes stimulated with Histoplasma capsulatum antigens.

Antimicrobial Agents and Chemotherapy
R H Alford, B B Cartwright

Abstract

Human peripheral blood lymphocytes stimulated with Histoplasma capsulatum yeasts were exposed in culture to graded concentrations of ketoconazole or amphotericin B and subsequently assessed for membrane integrity, thymidine uptake, and blastogenesis. Lymphocyte reactivity varied with concentration and duration of exposure to ketoconazole. Overt membrane toxicity resulted from exposure to 40 micrograms of ketoconazole per ml for 5 days, diminished thymidine uptake occurred with concentrations as low as 5 micrograms/ml, and 15 to 20 micrograms/ml caused a marked decrease in thymidine uptake and eventually diminished blastogenesis. The antilymphocyte action of ketoconazole was neutralized by increasing the concentration of human serum in cultures to 40% regardless of its cholesterol content. Amphotericin B activity was qualitatively similar but less pronounced.

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Citations

Jan 1, 1990·International Journal of Immunopharmacology·V VuddhakulY H Thong
Aug 1, 1992·International Journal of Immunopharmacology·M CoolsJ Van Wauwe
Nov 19, 2002·Clinics in Dermatology·Virendra N Sehgal, Sujay Khandpur
Jul 9, 2003·Critical Care Medicine·Sydney JacobsNasser Fawzan Al Omar
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Sep 1, 1987·Journal of the American Academy of Dermatology·J L Lesher, J G Smith
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