Journal of Antimicrobial Chemotherapy (2002) 49, 731-740
© 2002 The British Society for Antimicrobial Chemotherapy
A sub-inhibitory concentration of amphotericin B enhances candidastatic activity of interferon-
- and interleukin-13-treated murine peritoneal macrophages
1Laboratoire des Macrophages, Médiateurs de l’Inflammation et Interactions Cellulaires, UPRES-EA 2405, INSERM IFR 31, C.H.U., Rangueil, 1 avenue Jean Poulhès; 2Département de Parasitologie et Mycologie, Centre Hospitalier Universitaire, Hopital Rangueil, 1 avenue Jean Poulhès, 31403 Toulouse Cedex 4, France
Received 3 September 2001; returned 13 November 2001; revised 18 December 2001; accepted 4 January 2002.
We studied the effects of interferon-
(IFN-), 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-, 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- reduces the uptake process whereas the Th2 cytokines increase it. This difference is correlated to mannose receptor expression, which is decreased by IFN- but increased by the Th2 cytokines. So, the effects on phagocytosis and candidastatic activity of IFN--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-. Amphotericin B associated with IL-13 or IFN-, but not with IL-4, enhanced the yeast growth inhibition activity of macrophages. The ROIs were involved in the additive effect of IFN- 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.
* Corresponding author. Tel: +33-5-6132-2893; Fax: +33-5-6132-2293; E-mail: md.linas{at}toulouse.inserm.fr
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