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

Abstract

SUMMARY 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 (Tal)) 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 Tal 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 TQI 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 T α 1 and fluconazole is due lo a direct antifungal action and activation of the immunocompetence.

Thymax, a gross thymic extract, exerts cell cycle arrest and apoptosis in Ehrlich ascites carcinoma in vivo

“…Furthermore, patients with different malignancies have been treated with Tα1, including for lung [ 14 ] and renal cancer [ 15 ] and for melanoma [ 16 , 17 ]. Thymosin fraction 5 (TF5) inhibits growth of hematopoietic leukemia cell lines and neuroendocrine tumor cells [ 18 , 19 , 20 ], and thymic extracts have been found to exert immunomodulatory effects, including stimulation and/or maturation of T-cell differentiation [ 21 ] as well as the activation of dendritic cells (DC) [ 22 ] and natural killer (NK) cells [ 23 ].…”

Promising immunotherapy against fungal diseases

“…PMNs showed an increased intracellular killing of Candida (C.) albicans upon the combinatorial treatment with Tα1 and fluconazole in these mice [38]. These data suggest that Tα1 boosts neutrophils in combination with an antifungal drug to efficiently kill fungi, but in vivo data are still lacking.…”

“…The thymus-derived immune-stimulatory agent thymosin-α1, which is approved in more than 30 countries to treat viral infections and as an immune adjuvant [37], prolonged survival and reduced fungal burden in kidneys of immunosuppressed mice when used in combination with fluconazole [38]. PMNs showed an increased intracellular killing of Candida (C.) albicans upon the combinatorial treatment with Tα1 and fluconazole in these mice [38].…”