A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-γ-and interleukin-13-treated murine peritoneal macrophages

Abstract

We studied the effects of interferon-γ (IFN-γ), a Th1 cytokine, and interleukin-13 (IL-13) or interleukin-4 (IL-4), Th2 cytokines, on the antifungal activity of resident murine peritoneal macrophages against Candida albicans 'in vitro'. IFN-γ, IL-13 and IL-4 treatment enhanced the candidastatic functions of the macrophages. Reactive oxygen intermediates (ROIs) seem to be directly involved in the increase of anti-Candida activity in macrophages treated with Th1 or Th2 cytokines. Study of unopsonized C. albicans phagocytosis showed that IFN-γ reduces the uptake process whereas the Th2 cytokines increase it. This difference is correlated to mannose receptor expression, which is decreased by IFN-γ but increased by the Th2 cytokines. So, the effects on phagocytosis and candidastatic activity of IFN-γ-treated macrophages are dissociated. In contrast, the phagocytic ability of macrophages pretreated 'in vitro' with IL-4 or IL-13 played a complementary role to the ROIs, in reduction of yeast proliferation by macrophages. In consequence, the macrophages treated with IL-13 and IL-4 develop a higher fungistatic activity than macrophages activated by IFN-γ. Amphotericin B associated with IL-13 or IFN-γ, but not with IL-4, enhanced the yeast growth inhibition activity of macrophages. The ROIs were involved in the additive effect of IFN-γ with amphotericin B, whereas another mechanism was implicated in the increase of candidastatic activity of macrophages treated with IL-13 in association with amphotericin B.