Inhibition of anthralin-caused skin tumor promotion and interleukin-1 alpha production by potent immunosuppressant FK506.

The effect of FK506, a potent immunosuppressive agent, on 7,12-dimethylbenz[alpha]anthracene-initiated and anthralin-promoted skin tumor formation was examined in CD-1 mice. A topical application of 0.1 mumol FK506 to mouse skin 15 min prior to each anthralin treatment markedly inhibited skin tumor formation. Anthralin stimulated IL-1 alpha production in primary cultured mouse epidermal cells, and the peak IL-1 alpha level was observed at 6 h after the stimulation. Anthralin also stimulated IL-1 alpha release into culture medium. Both production and release of Il-1 alpha were markedly inhibited by FK506 (0.1 or 1 microM). FK506 (1 microM) alone neither affected IL-1 alpha production nor its release. It may be possible that the inhibition of IL-1 alpha production by FK506 is related to its anti-tumor-promoting action.