In human epidermis, basal keratinocytes are the main source of interleukin-1 (IL-1), and IL-1α is the predominant form, whereas IL-1β appears to exist predominantly in cultured keratinocytes. We investigated the effects of retinoic acid (RA) treatments on IL-1α and -β protein and mRNA expression of normal human keratinocytes cultured in low-calcium defined medium with or without hydrocortisone. Radioimmunoassay showed that after stimulation by RA, the IL-1β intracellular level is predominantly increased, with no significant modification of IL-1α expression. The addition of hydrocortisone in the culture medium resulted in a decrease in RA-induced IL-1β overexpression, without notable modifications in untreated cultures. Release of both IL-1α and -β in culture super-natants was detectable only after RA treatment and in the absence of hydrocortisone. The overexpression of IL-1β in control and RA-treated cultures mainly concerned the 52- and 31- to 36-kD biologically inactive precursor forms. Northern blot using specific IL-1α and -β oligonucleotide probes showed that IL-1β mRNA predominate over IL-1α mRNA and reach a maximal level 6 h before the IL-1β protein peak. These findings indicate that in cultured keratinocytes intracellular IL-1β is preferentially increased by RA but in its immature forms. The significance of this overexpression remains t