Modulation of delayed type hypersensitivity in mice treated with photoproducts of various photosensitizers used in photodynamic therapy.

Photodynamic therapy is frequently accompanied by the induction of immunosuppression. The photochemical mechanisms behind the induction of this immunosuppression are not clear. The purpose of this study was to evaluate the potential of photoproducts of merocyanine 540 (MC540), protoporphyrin IX (PPIX) and hematoporphyrin derivative (HpD) to cause modulation (suppression/activation) of the T cell immune response in vivo. The approach that we have adopted is the pre-irradiation of a photosensitizer solution with the subsequent application of the products of photosensitizer photodegradation in animals. In this approach the photochemical mechanisms of type I and II are not involved in the photosensitized modification of biological targets in vivo. Using the model of delayed type hypersensitivity (DTH) reaction to sheep red blood cells in mice, we have demonstrated that the photoproducts of three essentially different photosensitizers affect T-cell immunity. The HpD photoproducts had a suppressive effect on the DTH, while products of PPIX photodegradation enhanced the DTH nearly twice. Pre-irradiated MC540 strongly modulated the DTH response, i.e. the DTH was enhanced at low doses and inhibited at higher doses. Our results strongly indicate that at least part of the photodynamic therapy-induced immunomodulation may occur via the photobleaching of photosensitizers accompanied by the generation of photoproducts, which can affect T cell immunity.