Synergistic Effect of 5-Fluorouracil and Amphotericin B in Murine Paracoccidioidomycosis: Immune Modulation and Enhanced Fungal Clearance.

Paracoccidioidomycosis (PCM) is a systemic fungal infection that primarily affects the lungs. Previous studies have shown that 5-fluorouracil (5-FU), a chemotherapeutic agent, reduces pulmonary myeloid-derived suppressor cells (MDSCs), thereby stimulating immune responses in PCM. This study aimed to evaluate the efficacy of the combined 5-FU and AmB therapy in a murine model of PCM. C57BL/6 mice were infected with Paracoccidioides brasiliensis and treated with AmB and/or 5-FU. We found that the 5-FU and AmB combination therapy led to improved disease control, as evidenced by reduced fungal burden, decreased tissue damage, and an increased survival rate. Moreover, the combined treatment was associated with decreased lymphocyte and neutrophil counts, along with an increased number of macrophages in pulmonary tissue, suggesting a controlled infectious process without hyperinflammatory reactions. These findings support the potential of combining 5-FU with conventional antifungal therapy as a promising strategy for enhancing PCM treatment outcomes.