CYTOKINE RELEASE BY PERIPHERAL BLOOD MONONUCLEAR CELLS IS AFFECTED BY 8-METHOXYPSORALEN PLUS UV-A

Psoralen plus UV-A (PUVA) is an effective therapy for psoriasis but also 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. Peripheral blood mononuclear cells (PBMC) obtained from humans were incubated with 8-methoxypsoralen (8-MOP) and exposed to UV-A (20 kJ/m2). This treatment resulted in a significant reduction of IL-6 and IL-8 amounts in the supernatants. In addition, an inhibition of IL-1 beta and TNF alpha production by lipopolysaccharide (LPS)-stimulated PBMC was observed upon PUVA treatment. Accordingly, northern blot analysis showed decreased levels of mRNA encoding for IL-1 beta, IL-6, IL-8 and TNF alpha in PUVA-treated PBMC. Finally PBMC were obtained from psoriatics undergoing oral photochemotherapy before the beginning and after completion of treatment. The PBMC collected after PUVA spontaneously produced significantly less IL-6 and IL-8 in comparison to the respective samples obtained before therapy. A similar suppression of IL-1 beta and TNF 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 production of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha by PBMC. Because these cytokines are important in the mediation of inflammatory reactions, one may speculate that the inhibitory effects could contribute to the antiinflammatory activity of PUVA.