Systemic administration of etretin increases epidermal interleukin I in the rat

We have studied the effect of systemic administration of etretin (Ro 10-1670) on the epidermal interleukin I (ILI) pool in the rat. Hairless rats were given varying doses of etretin intraperitoneally for 21 days, or a fixed dose for 2, 8 and 16 days. Abdominal skin was taken and processed for light microscopy, autoradiography (using [3H]-thymidine) and ILI assays. ILI was assayed in supernatants of epidermal extracts by both the lymphocyte activating factor (LAF) assay and the stimulation of prostaglandin E2 (PGE2) release from dermal fibroblasts. A significant increase in both LAF and PGE2 stimulatory activities was found during etretin administration. After 21 days' treatment with varying doses there was a two- to three-fold increase as compared to the controls, with a peak at 2 and 5 mg/kg. At a fixed dose a two-fold increase was found after 2 days and a three- to four-fold increase after 16 days; normal pretreatment values were restored 16 days after cessation of etretin. This is the first demonstration in vivo that a retinoid can modulate ILI content in a tissue. As epidermal ILI has been found to be decreased in psoriasis, its modulation by retinoids might have therapeutic significance.