Effects of anidulafungin and voriconazole, singly and in combination, on cytokine/chemokine production by human monocyte-derived macrophages infected with Candida glabrata or activated by lipopolysaccharide

Background: Candida glabrata causes infections associated with severe sepsis, production of high concentrations of cytokines/chemokines, and high mortality. This study describes the effects of anidulafungin (ANF) and voriconazole (VRC), singly and in combination, on the production of eight cytokines/chemokines by human monocyte-derived macrophages (MDM) infected with C. glabrata or activated by lipopolysaccharide (LPS).

Methods: MDM monolayers were established, infected with C. glabrata or activated with LPS, and then treated with high or low concentrations of ANF, VRC, or both. Cytokine/chemokine levels in MDM supernatants were determined.

Results: Levels of cytokines/chemokines were significantly elevated in supernatants of infected or LPS-activated MDM. Except for interleukin-10, all significant decreases in cytokine/chemokine concentrations (p < 0.01) occurred in supernatants of infected MDM treated with high concentrations of ANF or ANF + VRC.

Conclusions: Decreases in cytokine/chemokine levels in supernatants of infected MDM treated with high concentrations of ANF or ANF + VRC suggest that similar treatment could improve survival in patients with severe, invasive C. glabrata infections and markedly elevated levels of serum cytokines/chemokines.