Anticryptococcal effect of amphotericin B is mediated through macrophage production of nitric oxide

Masaki Tohyama, Kazuyoshi Kawakami, Atsushi Saito

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Amphotericin B (AmB) is a classical antifungal drug and one of the must effective antifungal drugs for the treatment of systemic fungal infection. It is also known to have various immunomodulating activities other than its direct antifungal effect. In the present study, we demonstrated that AmB augmented gamma interferon (IFN-γ)-induced killing potentials of murine peritoneal macrophages against Cryptococcus neoformans in a dose-dependent manner. This effect was strongly blocked by N(G)-monomethyl-L-arginine, a competitive inhibitor of nitric oxide (NO) synthesis. In addition, AmB markedly augmented macrophage NO production induced by IFN-γ with a dose- response curve similar to that seen with its effect on the anticryptococcal activity. These effects were partially mediated by either tumor necrosis factor alpha or interleukin-1, because AmB enhanced IFN-γ-induced production of these cytokines by macrophages and their specific antibodies partially inhibited the AraB-induced enhancement of NO generation when they were used separately. Our results indicate that AmB induces the production of tumor necrosis factor alpha and IL-1 by macrophages and augments their anticryptococcal activity through triggering the NO-dependent pathway.

Original languageEnglish
Pages (from-to)1919-1923
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume40
Issue number8
DOIs
Publication statusPublished - 1996 Aug

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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