UVA-induced inhibition of proliferation of PHA-stimulated lymphocytes from humans treated with 8-methoxypsoralen.
Lymphocytes from healthy human donors were used as a model system for studying the combined effect of 8-methoxypsoralen (8-MOP) plus UVA. Two hours after oral administration of therapeutic doses of the drug enough 8-MOP was taken up in vivo by the circulating peripheral lymphocytes to cause significant inhibition of phytohaemagglutinin induced lymphocyte proliferation when the cells were exposed in vitro to UVA irradiation. The inhibition of proliferation as monitored by a reduced 3H-thymidine incorporation into cellular DNA was shown to be UVA-dose dependent. Control cultures of 8-MOP containing lymphocytes which were not UVA irradiated showed normal blast transformation. In lymphocytes obtained from the same donors prior to 8-MOP intake, PHA-induced lymphocyte transformation was not impaired by UVA irradiation. In 8-MOP containing lymphocytes exposed repeatedly to UVA during the 72 h culture period a cumulative effect of irradiation could be observed. A varying sensitivity towards 8-MOP plus UVA was noted when the cells were irradiated at different times after PHA stimulation. The cells were most vulnerable to UVA irradiation during the DNA-synthesis phase of the proliferating lymphocytes. The results suggest that dermal inflammatory infiltrates containing locally proliferating lymphocytes are influenced by systemic photochemotherapy since UVA penetrates well into the dermis.