Treatment with
8-methoxypsoralen (8-MOP) and ultraviolet A light (UVA) has been reported to modulate
cytokine production in various cells. Our study was conducted to see the effects of
8-MOP/UVA on the expression/production of
cytokines in peripheral blood lymphocytes and monocytes in relation to the therapeutic mechanisms of
extracorporeal photochemotherapy.
8-MOP/UVA augmented the expression of mRNAs for
interferon-gamma (IFN-gamma) and
interleukin (IL)-2 and reduced those for
IL-4 and
IL-10 in peripheral blood mononuclear cells (PBMCs) from normal subjects and Sézary syndrome patients. This enhancement of Th1
cytokines was caused by increment of
cytokine production by Th1 cells but not by conversion of Th2 cells to produce Th1
cytokines. The number of IFN-gamma-secreting lymphocytes was markedly increased in
8-MOP/UVA-treated PBMCs 20 h
after treatment, and its amount was elevated in culture supernatants. However, this enhanced production of IFN-gamma was found only until three days after
8-MOP phototreatment, and its level was rapidly declined by five days
after treatment. In addition to this Th1-polarized action,
8-MOP/UVA-treated PBMCs produced enhanced amounts of
IL-8 upon stimulation with anti-CD3/CD28
antibodies. Phototreated CD4+ but not CD8+ cells provided excellent T cell help for monocytes to produce
IL-8 via a direct cell-to-cell contact mechanism. These findings suggest that
8-MOP/UVA has a transient but biologically active Th1-skewing action in T cells, and the phototreated T cells simultaneously stimulate monocytes to produce
IL-8. It is suggested that
8-MOP/UVA exerts a beneficial
therapeutic effect on malignant Th2
neoplasms as a Th1-skewing
cytokine modifier and that 8-MOP-phototreated CD4+ T cells allow monocytes to become effective
tumor antigen-presenting cells for
tumor-specific cytotoxic T cells.