The anti-fungal agent itraconazole exerts immunosuppressive effects on alloreactivity but not on natural immunity in vitro.
The anti-fungal azole drug itraconazole was compared with fluconazole regarding immunosuppressive effects in a model of human alloreactivity in vitro (the mixed lymphocyte culture, MLC) and in assays of non-adaptive immunity (natural killing, NK, and lymphokine activated killing, LAK). Itraconazole, but not fluconazole, strongly inhibited lymphocyte proliferation and the generation of allospecific cytolytic activity, but had no effect on the development of major histocompatibility complex (MHC)-unrestricted ("natural killer-like") cytotoxicity or of alloindifferent suppressive activity in MLC. Neither drug blocked LAK cell induction, nor the effector phase of either NK or LAK activity. These results suggest that itraconazole might represent a new class of immunosuppressive agent which specifically blocks alloreactivity without affecting natural immunity.
Pawelec
G
G
Second Department of Internal Medicine, University Medical Clinic, Tübingen, F.R.G.
Jaschonek
K
K
Ehninger
G
G
D000935:Antifungal Agents / Q000494:pharmacology; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D017964:Itraconazole; D015725:Fluconazole; D007654:Ketoconazole