Combined effect of fluconazole and thymosin α1 on systemic candidiasis in mice immunosuppressed by morphine treatments

Treatment of systemic infection with Candida albicans with a combination of an antifungal agent (i.e. fluconazole) and a thymus-derived immunostimulant (i.e. thymosin α1 (Tα1) in mice immunosuppressed by morphine treatments was investigated. In normal mice, fluconazole given after infection with 10⁶ C. albicans cells was more effective than in mice treated with morphine. Combination treatment with fluconazole and Tα1 prolonged survival and reduced the fungal burden in the kidneys of immunosuppressed mice. We also investigated the influence of this combined treatment on killing properties of polymorphonuclear leucocytes (PMN) and natural killer (NK) cell activity, inhibited by morphine administrations. Treatment with Tal or fluconazole as single agents promoted a recovery of normal NK cell activity and intracellular killing of C. albicans by PMN, while the combination significantly increased both of these responses, probably through the modulation of lymphokine production. Our data suggest that the additive effect of Tα1 and fluconazole is due to a direct antifungal action and activation of the immunocompetence.