We hypothesized that the effects of extracorporeal photopheresis (ECP) are mediated by induction of immunosuppressive cytokines like IL-10, which enhances synthesis of HLA-G molecules. HLA-G products are expressed by CD14+ peripheral blood mononuclear cells (PBMC) and play an important role in inhibition of cell mediated immunity. ECP induces apoptosis in lymphocytes but not in CD14+ cells. We, therefore, investigated the concentrations both of IL-10 and of soluble HLA-G5/sHLA-G1 molecules in supernatants from cultures of lipopolysaccharide-stimulated PBMC obtained from leukocyte collection bags of 10 patients receiving ECP for graft versus host disease both before (pre-irradiation) and after (post-irradiation) exposure to 8-methoxypsoralen and UVA irradiation. Levels of both IL-10 and HLA-G5/sHLA-G1 molecules were increased in the post-irradiation cultures. This suggests that therapeutic effects of ECP could be mediated by increased production of IL-10 and tolerogenic HLA-G molecules.
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