Document 0102
 DOCN  M9580102
 TI    Synergic inhibitory activity of amphotericin-B and gamma interferon
       against intracellular Cryptococcus neoformans in murine macrophages.
 DT    9506
 AU    Herrmann JL; Dubois N; Fourgeaud M; Basset D; Lagrange PH; Laboratoire
       de Microbiologie, Hopital Hotel Dieu, Paris, France.
 SO    J Antimicrob Chemother. 1994 Dec;34(6):1051-8. Unique Identifier :
       AIDSLINE MED/95247623
 AB    Cryptococcus neoformans is responsible for pulmonary and meningal
       infections in HIV patients. The lack of effective cellular cooperation
       caused by the low level of CD4+ cells, and the resistance of C.
       neoformans to phagocytosis allows growth and persistence of the yeast in
       the host. We describe here an in-vitro model of intracellular
       replication of C. neoformans inside J774-A.1 macrophages, and the
       determination of the intracellular antifungal activity of amphotericin B
       and fluconazole alone or in association with IFN-gamma. The maximum
       inhibitory effect was observed with one MIC of amphotericin B and 100 or
       1000 IU/mL of IFN-gamma. amphotericin B alone (at 1 x MIC), or either 1
       x or 50 x MIC of fluconazole in normal or IFN-gamma activated
       macrophages, did not eradicate the ingested yeast. A potential
       underlying mechanism of the synergy of amphotericin B in IFN-gamma
       primed macrophages was investigated by measurement of nitrite level and
       by use of the NO synthase competitive inhibitor, NG-monomethyl
       L-arginine (NMMA). One MIC of amphotericin B was able to activate the
       synthesis of nitrogen reactive intermediates in IFN gamma-primed
       macrophages. NMMA treated infected macrophages responded less well to
       IFN-gamma priming, resulting in a moderate inhibition in subsequent
       amphotericin B exposure.
 DE    Amphotericin B/*PHARMACOLOGY  Animal  Cells, Cultured  Cryptococcus
       neoformans/*DRUG EFFECTS/METABOLISM  Drug Synergism
       Fluconazole/PHARMACOLOGY  Human  Interferon Type II/*PHARMACOLOGY
       Macrophages/DRUG EFFECTS/*MICROBIOLOGY  Mice  Microbial Sensitivity
       Tests  Nitric Oxide/ANTAGONISTS & INHIB/BIOSYNTHESIS  Support, Non-U.S.
       Gov't  JOURNAL ARTICLE

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