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

J Antimicrob Chemother. 2002 May;49(5):731-40. doi: 10.1093/jac/dkf011.

Abstract

We studied the effects of interferon-gamma (IFN-gamma), 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-gamma, 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-gamma reduces the uptake process whereas the Th2 cytokines increase it. This difference is correlated to mannose receptor expression, which is decreased by IFN-gamma but increased by the Th2 cytokines. So, the effects on phagocytosis and candidastatic activity of IFN-gamma-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-gamma. Amphotericin B associated with IL-13 or IFN-gamma, but not with IL-4, enhanced the yeast growth inhibition activity of macrophages. The ROIs were involved in the additive effect of IFN-gamma 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.

MeSH terms

  • Amphotericin B / pharmacology*
  • Animals
  • Antifungal Agents / pharmacology*
  • Antioxidants / pharmacology
  • Candida albicans / drug effects*
  • Cell Division / drug effects
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Female
  • In Vitro Techniques
  • Indicators and Reagents
  • Interferon-gamma / pharmacology*
  • Interleukin-13 / pharmacology*
  • Interleukin-4 / pharmacology
  • Lectins, C-Type*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / microbiology
  • Mannose Receptor
  • Mannose-Binding Lectins*
  • Mice
  • Nitric Oxide / pharmacology
  • Phagocytosis / drug effects
  • Receptors, Cell Surface / metabolism
  • Respiratory Burst / drug effects
  • Uracil / metabolism

Substances

  • Antifungal Agents
  • Antioxidants
  • Cytokines
  • Indicators and Reagents
  • Interleukin-13
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Interleukin-4
  • Nitric Oxide
  • Uracil
  • Amphotericin B
  • Interferon-gamma