Inhibition of Mixed Leukocyte Culture Reaction by 8-Methoxypsoralen and Long-wavelength Ultraviolet Radiation

Abstract

Psoriasis patients receiving therapy with oral 8-methoxypsoralen plus long-wavelength ultraviolet radiation have been reported to have diminished leukocyte DNA synthesis and immune reactivity. In order to quantitate the immunological effects of therapeutic concentrations of 8-methoxypsoralen plus long-wavelength ultraviolet radiation, we measured the mixed leukocyte culture reaction in vitro . Leukocytes treated with 8-methoxypsoralen were exposed to plate glass filtered ultraviolet radiation from a bank of PUVA fluorescent lamps. To evaluate the (two-way) mixed leukocyte reaction, treated leukocytes were mixed with untreated leukocytes from another donor in microtiter wells and tritiated thymidine incorporation was measured after 4 to 6days. To measure stimulation or proliferation ability (one-way mixed leukocyte reactions), treated or untreated leukocytes were exposed to 2000R X-radiation prior to mixing. Treatment of leukocytes with 8-methoxypsoralen (0.01, 0.1, or 1.0 μ g/ml) followed by 7,000 to 87,000 J/m 2 long-wavelength ultraviolet radiation resulted in a dose dependent inhibition of mixed leukocyte culture reactivity. 0.1 μ g/ml 8-methoxypsoralen plus 7,000 J/m 2 ultraviolet radiation resulted in a 48% reduction ( p μ g/ml 8-methoxypsoralen plus 87,000 J/m 2 ultraviolet radiation virtually abolished reactivity in the two-way mixed leukocyte reaction and in both one-way mixed leukocyte reactions. Exposure to 87,000 J/m 2 long wavelength ultraviolet radiation alone resulted in 45% inhibition ( p in vitro .