346 KETOCONAZOLE, AMPHOTERICIN B AND AMPHOTERICIN METHYL ESTER: COMPARATIVE IN-VITRO AND IN-VIVO TOXICOLOGICAL EFFECTS ON IMMUNE FUNCTION

Abstract

We have previously found that antifungal agents used in the treatment of patients with immune dysfunctions have enhanced those abnormalities and may have rendered the patients more susceptible to secondary infections. To examine the role that anti-fungal agents play in producing such immune dysfunction, we investigated a number of parameters for host defense following invitro addition of the antifungal agents ketoconazole, amphotericin B (AMB), and amphotericin B methyl ester (AME). Similar assays were repeated before and after the patients had received these drugs.

Viability by trypan blue exclusion, adherence by glass bead column, chemotaxis by under agarose technique and phagocytosis and killing by NBT, chemiluminescence and acridine orange direct visualization were assayed. In striking contrast to AMB and AME, ketoconazole showed no significant effect on neutrophils. Adherence in the presence of therapeutic plasma levels of AMB and AME were decreased at low drug concentrations while at higher concentrations, adherence was increased. The chemotactic responses of cells incubated with AMB and AME showed marked suppression and phagocytosis and killing appeared slightly decreased as compared to control assays and assays done in the presence of ketoconazole. In summary, our data suggest that ketoconazole is less toxic to functioning neutrophils than AMB or AME and may offer a therapeutic advantage over the latter drug.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD