title: Suppression of neutrophil and lymphoproliferative responses in vitro by itraconazole but not fluconazole.
abstract: Itraconazole and fluconazole are triazole compounds recently licensed for the therapy of systemic fungal infections. At 10 micrograms/ml concentrations, itraconazole was found to suppress neutrophil chemotaxis, random movement, deoxyglucose uptake and hexose-monophosphate shunt activity to the same extent as ketoconazole, an older generation azole antifungal. Itraconazole was also found to suppress mitogen-induced lymphocyte transformation to the same extent as ketoconazole at concentrations as low as 1 microgram/ml. By contrast, significant inhibition of both neutrophil and lymphocyte functions was not observed with fluconazole at concentrations as high as 50 micrograms/ml. These results suggest that fluconazole may be less immunotoxic than itraconazole, and may be more suitable for use in immunocompromised patients.
authors.affiliation: Department of Child Health, University of Queensland, Mater Public Hospital, South Brisbane, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Vuddhakul
authors.forename: G T
authors.initials: GT
authors.lastname: Mai
authors.forename: J G
authors.initials: JG
authors.lastname: McCormack
authors.forename: W K
authors.initials: WK
authors.lastname: Seow
authors.forename: Y H
authors.initials: YH
authors.lastname: Thong
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003847:Deoxyglucose / Q000493:pharmacokinetics; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D017964:Itraconazole; D015725:Fluconazole; D003847:Deoxyglucose; D007654:Ketoconazole