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Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
The effects of fluconazole and cytokines on human mononuclear cells
Isil Fidan1, Sevgi Yuksel, Turgut Imir
1Department of Medical Microbiology, Gazi University, Ankara, Turkey. isilfidan@yahoo.com
Abstract:
Candida infections are common infections and fluconazole is one of the most frequently administered antifungal agents in their treatment. The resistance developed against antifungal agents has necessitated the improvement of new treatments. This study focuses on the investigation of the effect of fluconazole and cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF) on chemokine production and anticandidal activity of human monocytes. In the study it was observed that GM-CSF caused an increase in candidacidal activity of monocytes. Anticandidal activity of GM-CSF + IFN-gamma combination was not found to be more effective than GM-CSF or IFN-gamma alone. The presence of cytokine and fluconazole caused an increase in the levels of CCL3 and CCL4 chemokines. Accordingly, it was considered that chemokines could contribute to the efficacy of fluconazole in C. albicans infections. Besides, in order to strengthen the immune system some cytokines might be used in addition to antifungal agents for the treatment.
Insights
This study shows that cytokines like GM-CSF enhance monocyte killing of Candida. Combining fluconazole with cytokines boosts specific chemokine production, potentially improving antifungal treatment efficacy.
Area of Science:
- Immunology
- Mycology
- Pharmacology
Background:
- Candida infections are prevalent, with fluconazole being a primary antifungal treatment.
- Rising antifungal resistance necessitates novel therapeutic strategies.
- Understanding host-pathogen interactions and immune modulation is crucial for improving Candida infection outcomes.
Purpose of the Study:
- To investigate the impact of fluconazole and key cytokines (IFN-gamma, TNF-alpha, GM-CSF) on human monocyte function.
- To assess the effects on chemokine production (CCL3, CCL4) and anticandidal activity.
- To explore potential synergistic effects for enhanced therapeutic strategies.
Main Methods:
- Human monocytes were treated with fluconazole and/or cytokines (IFN-gamma, TNF-alpha, GM-CSF).
- Anticandidal activity was measured by assessing the monocytes' ability to kill Candida.
- Chemokine levels (CCL3, CCL4) were quantified in response to treatments.
Main Results:
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly enhanced the candidacidal activity of monocytes.
- Combination therapy of GM-CSF with interferon-gamma (IFN-gamma) did not show superior anticandidal effects compared to individual treatments.
- Fluconazole combined with cytokines led to increased production of chemokines CCL3 and CCL4.
Conclusions:
- Chemokines CCL3 and CCL4 may play a role in augmenting the efficacy of fluconazole against Candida albicans.
- Cytokines, particularly GM-CSF, show promise in enhancing the innate immune response against Candida infections.
- Adjunctive therapy with specific cytokines alongside antifungal agents could be a viable strategy to bolster the immune system in treating Candida infections.

