FK506 (tacrolimus) inhibition of intracellular production and enhancement of interleukin 1alpha through glucocorticoid application to chemically treated human keratinocytes.

PURPOSE: Production of the proinflammatory cytokine interleukin (IL) 1alpha, which is stored in keratinocytes (KCs) and is multifunctional, may be enhanced by glucocorticoids. A study was made to confirm whether immunosuppressants such as the macrocyclic lactone FK506 (tacrolimus) possibly serve to modulate glucocorticoid- stimulated IL-1alpha production from chemically treated KCs.

METHODS

Using cultured human KCs, the effects of FK506 on the production of IL-1alpha treated with chemicals (trinitrobenzene sulfonic acid sodium salt, TNBS) plus hydrocortisone were analyzed by ELISA and mRNA expression of IL-1alpha using RT-PCR.

RESULTS

Intracellular IL-1alpha in TNBS-treated human KCs was increased with a low concentration of 10(-10)M of hydrocortisone. Further FK506 application inhibited significantly this increased production. The mRNA expression of IL-1alpha at various concentrations of chemicals was not remarkably different.

CONCLUSIONS

FK506may control the increase in IL-1alpha with glucocorticoid in KCs, suggesting FK506 to suppress harmful effects of glucocorticoids such as steroid rosacea.