CYTOKINE RELEASE BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS IS AFFECTED BY8-METHOXYPSORALEN PLUS UV-A

Psoralen plus UV-A (PUVA) is an effective therapy for psoriasis but al so for other inflammatory dermatoses. The precise mechanisms of action , however, are not absolutely clear. Therefore, the effect of PUVA on the release of the proinflammatory cytokines interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor alpha (TNF alpha) was studied. Periphe ral blood mononuclear cells (PBMC) obtained from humans were incubated with 8-methoxypsoralen (8-MOP) and exposed to UV-A (20 kJ/m(2)). This treatment resulted in a significant reduction of IL-6 and IL-8 amount s in the supernatants. In addition, an inhibition of IL-1 beta and TNF alpha production by lipopolysaccharide (LPS)-stimulated PBMC was obse rved upon PUVA treatment. Accordingly, northern blot analysis showed d ecreased levels of mRNA encoding for IL-1 beta, IL-6, IL-8 and TNF alp ha in PUVA-treated PBMC. Finally PBMC were obtained from psoriatics un dergoing oral photochemotherapy before the beginning and after complet ion of treatment. The PBMC collected after PUVA spontaneously produced significantly less IL-6 and IL-8 in comparison to the respective samp les obtained before therapy. A similar suppression of IL-1 beta and TN F alpha by in vivo PUVA was found in LPS-stimulated PBMC. The present data demonstrate that PUVA both in vitro and in vivo suppresses the pr oduction of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TN F alpha by PBMC. Because these cytokines are important in the mediatio n of inflammatory reactions, one may speculate that the inhibitory eff ects could contribute to the antiinflammatory activity of PUVA.