SCHNEBLE HM, JONAS D, ENGELS I, DASCHNER FD, FRANK U; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 555 (abstract no. 699).
Inst. of Environmental Med., Univ. Hosp. Freiburg Med. Sch., Freiburg, GERMANY.
BACKGROUND: Interactions with the host immune defense system are important for understanding both the efficacy and the side effects of antifungal agents. Of the agents available at present, it is unclear as to whether amphotericin B (AMB) improves or impairs the function of phagocytes, while recent studies show that fluconazole (FLC) may increase the killing of germs by phagocytes. This study was conducted because, as yet, there are no data available on the effects of the echinocandin LY303366 on phagocytosis, oxidative burst and killing of germs by human phagocytes.METHODS: Heparinized whole blood from 13 healthy volunteers was preincubated for 30 min with either 3.8 microg/ ml LY303366, 2.0 microg/ml AMB or 6.7 microg/ml FLC. Yeast cells were added to the assay and incubated at 37 degrees for 30 min and 2h. One assay containing no antifungal agent served as control. Following incubation, samples were analyzed by flow cytometry. To measure phagocytosis, yeast cells were stained with calcein-acetoxymethyl ester (calcein-AM). Burst-reaction was detected by oxidation of dihydroethidium. For the killing-assay, dead yeast cells were counterstained with ethidiumhomodimer-1. For statistical analysis, the Wilcoxon-test was used.RESULTS: When cells were preincubated with LY303366 or FLC, phagocytosis and oxidative burst were not influenced. Intracellular killing, however, increased significantly after 2 hours of incubation (+70.7% and +19.4%, respectively; p<0.01). In contrast, preincubation with AMB decreased both phagocytosis and oxidative burst significantly (after 30 min of incubation: -7.2% and -6.9%, respectively; p<0.01). AMB showed a tendency toward impairing intracellular killing (-12.8%; p = 0.15).CONCLUSION: In our model, therapeutic concentrations of LY303366 and FLC improved intracellular killing of C. albicans without influencing phagocytosis or oxidative burst. In contrast, AMB impaired phagocytic functions.
Publication Types:
Keywords:
- Amphotericin B
- Animals
- Antifungal Agents
- Antigens, Fungal
- Candida albicans
- Cytoplasm
- Flow Cytometry
- Fluconazole
- Humans
- Peptides, Cyclic
- Phagocytes
- Phagocytosis
- Respiratory Burst
- Yeasts
- anidulafungin
- immunology
Other ID:
UI: 102246785
From Meeting Abstracts