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

## TL;DR

Combining 5-fluorouracil with Amphotericin B improves treatment outcomes in a mouse model of a fungal lung disease by boosting immune responses and reducing infection.

## Contribution

This study demonstrates that combining 5-fluorouracil with Amphotericin B enhances fungal clearance and survival in a murine model of PCM.

## Key findings

- Combination therapy reduced fungal burden and tissue damage in infected mice.
- The treatment increased survival rates and modulated immune cell populations in the lungs.
- The combination showed controlled immune responses without causing hyperinflammation.

## Abstract

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.