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In-vitro effects of cilofungin (LY121019), amphotericin B and amphotericin B-deoxycholate on human polymorphonuclear
1Service de Médecine Interne, Institut Jules Bordet, Bruxelles, Belgium.
Abstract:
The in-vitro influence of cilofungin (LY121019) and amphotericin B on human polymorphonuclear leucocytes (PMNs) was studied by a multifunctional approach. Cilofungin at high concentration (greater than or equal to 20 mg/l) increased adherence to plastic and ingestion of Staphylococcus aureus by PMNs in suspension and Candida albicans by adherent PMNs, and slightly decreased MTT reduction and superoxide generation. Amphotericin B and amphotericin B-deoxycholate decreased adherence to plastic (IC50: 5.1 and 8.2 mg/l respectively) and superoxide generation induced by PMA and opsonized zymosan (IC50 1.1 mg/l for amphotericin B-deoxycholate). Variable results were observed for intra-cellular killing and ingestion. The functional assessment was made with four clinical isolates of yeasts (Can. albicans, Can. tropicalis, Can. Torulopsis) (glabrata, Cryptococcus neoformans). The inoculum was preincubated with the antifungals (PRE) or they were added during (PER) or after ingestion (POST) using PMNs in suspension (PRE and PER), or adhering to plastic (PRE, PER and POST). With the scheme PRE, killing was usually increased with amphotericin B-deoxycholate and cilofungin. With Crypt. neoformans, ingestion was also increased by the antifungals and sodium-deoxycholate, probably by altering the capsule. The results of the scheme POST showed that amphotericin B-deoxycholate, but not cilofungin, increased intracellular killing of Can. albicans, Can. tropicalis and Can. glabrata.
Insights
Cilofungin and amphotericin B affect human immune cells (PMNs) differently. Cilofungin enhances phagocytosis of bacteria and fungi, while amphotericin B impairs immune cell adherence and superoxide generation.
Area of Science:
- Immunology
- Pharmacology
- Mycology
Background:
- Human polymorphonuclear leucocytes (PMNs) are crucial for innate immunity.
- Antifungal agents like cilofungin and amphotericin B can modulate immune cell function.
- Understanding these interactions is vital for optimizing antifungal therapy.
Purpose of the Study:
- To investigate the in vitro effects of cilofungin and amphotericin B on human PMN functions.
- To compare the impact of these antifungals on PMN adherence, ingestion, killing, and oxidative burst.
- To assess these effects against various fungal and bacterial pathogens.
Main Methods:
- Multifunctional in vitro assessment of human PMNs.
- Exposure of PMNs to cilofungin and amphotericin B at various concentrations and time points (PRE, PER, POST).
- Evaluation of PMN adherence, Staphylococcus aureus and Candida albicans ingestion, intracellular killing, MTT reduction, and superoxide generation.
Main Results:
- High-concentration cilofungin enhanced PMN adherence and ingestion of S. aureus and C. albicans.
- Amphotericin B and its deoxycholate formulation reduced PMN adherence and superoxide generation.
- Both antifungals increased killing of yeasts when added before or during ingestion; amphotericin B-deoxycholate also increased killing when added after ingestion.
Conclusions:
- Cilofungin demonstrates immunomodulatory effects, potentially enhancing PMN antifungal activity.
- Amphotericin B exhibits immunosuppressive properties by reducing PMN adherence and oxidative burst.
- The timing of antifungal administration significantly influences their impact on PMN-mediated host defense.