Amphotericin B activation of human genes encoding for cytokines

Amphotericin B has been shown to cause release of cytokines, including interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), from monocytes and macrophages, Human and murine monocytic cell lines were used to evaluate the effects of amphotericin B on the transcription of IL-1 alpha, IL-1 beta, and TNF-alpha and the transcription and production of soluble IL-1 receptor antagonist (sIL-1Ra). The effects of inhibitors of transcription and translation on amphotericin B-induced IL-1 beta expression in a human monocytic cell line were also evaluated, Amphotericin B markedly increased IL-1 beta and TNF-alpha mRNA levels, with peak levels occurring by 4 h. Amphotericin B induced production of sIL-1Ra in a dose-dependent fashion and induced sIL-1Ra mRNA, with peak levels at 24 h, Cycloheximide and actinomycin D resulted in a dose-dependent decrease in amphotericin B-induced IL-1 beta expression at 2 h. Thus, amphotericin B induces gene expression for IL-1 beta, TNF-alpha, and IL-1Ra in human and murine monocytic cells.