Differential Induction of IL-12 p40 and IL-10 mRNA in Human Langerhans' Cells and Keratinocytes by in Vivo Occlusion, Vehicle, and All-TRANS Retinoic Acid

Background: Hydration and pharmacologic manipulation of the skin may have immunomodulatory effects. For instance, retinoic acid (RA) in vivo upregulates antigen-presenting cell (APC) activity of Langerhans' cells (LC). Objective: Our study was to determine whether RA increases LC APC activity via alteration of the potent immunoregulatory and reciprocally acting cytokines, IL-12 and IL-10. Methods: 0.1% RA and vehicle solvent only (V) as a control were applied under occlusion on the skin of normal volunteers. Freshly selected CD1a + LC and keratinocytes from keratome were subject to semiquantitative determination of IL-12 p40 and IL-10 mRNA levels. IL-12 p40 protein was measured by radioimmunoassay. Results: Occlusion alone and open vehicle alone did not induce LC immunoregulatory cytokines; LCs demonstrated significant induction of IL-12 p40 mRNA, when the vehicle was occluded for 48 hours and, to a lesser extent, IL-10 as well. IL-12 p40 mRNA could be further induced by RA-LC at the 20-hour time point; however, IL-10 mRNA was induced at the 48-hour time point. Neither occlusion nor RA significantly induced IL-12 p40 or IL-10 mRNA in CD1a keratinocytes at any time points. Conclusion: A tight reciprocal regulation of IL-10 and IL-12 is present in LCs and is consistent with the initial, but self-limited, inflammatory effect of occlusion and topical retinoids.