Treatment of peripheral blood mononuclear cells with 8-methoxypsoralen plus ultraviolet a radiation induces a shift in cytokine expression from a Th1to a Th2 response

Treatment with 8-methoxypsoralen plus ultraviolet A radiation and extracorp oreal photochemotherapy (photopheresis) are widely used for the treatment o f psoriasis and other inflammatory skin diseases, graft-versus-host disease , and mycosis fungoides. As the ratio of Th1 and Th2 cells appears to be cr itical for pathogenesis and progression of these disorders the effect of ps oralen plus ultraviolet A on Th1 and Th2 cytokine production by CD4+ lympho cytes was investigated. Human peripheral blood lymphocytes were incubated i n the presence of anti-CD3, rh-IL2, and rh-IL4 for 48 h. After subsequent s timulation with rh-IL2 and rh-IL4 for 72 h cells were treated with 8-methox ypsoralen (100, 500, 1000 ng per ml) plus ultraviolet A (2 J per cm(2)) and incubated for a further period of 5 h in the presence of iono- mycine, pho rbol-12-myristate acetate and monensin. Fluorescence-activated cell sorter analysis revealed a significant reduction of interleukin-2- and interferon- gamma -producing CD4+ cells upon psoralen plus ultraviolet A treatment depe nding on the concentration of 8-methoxypsoralen. In contrast, interleukin-4 -producing CD4+ cells were increased, indicating a shift from Th1 to a Th2 cell cytokine profile upon psoralen plus ultraviolet A treatment. These res ults indicate that 8-methoxypsoralen photochemotherapy of lymphocytes is ab le to modulate their Th1/Th2 distribution. Inhibition of Th1 cytokine expre ssion by psoralen plus ultraviolet A might help to explain its beneficial e ffects in the treatment of Th1 dominated skin diseases.