title: IL-10 does not play a role in cutaneous Photofrin photodynamic therapy-induced suppression of the contact hypersensitivity response.
abstract: Photodynamic therapy (PDT) treatment of both malignant and benign skin diseases has proven to be effective, and its use is increasing worldwide. However, preclinical studies using murine models have shown that PDT of the skin inhibits cell-mediated immune reactions, as measured by the suppression of the contact hypersensitivity (CHS) reaction. We have previously demonstrated that PDT enhances IL-10 expression in treated skin, and that the kinetics of induction of IL-10 is similar to the kinetics of suppression of systemic CHS reactions by cutaneous PDT. In the following report we have expanded upon these studies to demonstrate that cutaneous PDT, using Photofrin, induces elevated levels of systemic IL-10 that persist for at least 28 days following treatment. The increase in systemic IL-10 correlates to a prolonged suppression of CHS of at least 28 days following cutaneous PDT. IL-10 has been implicated as the causative agent in the suppression of cell-mediated immune reactions by UVB and transdermal PDT. However, in the studies reported here we demonstrate that the suppression of CHS by cutaneous PDT occurs via an IL-10 independent mechanism, as administration of anti-IL-10 antibodies had no effect on the ability of PDT to induce CHS suppression. These results were further confirmed using IL-10 knockout (KO) mice. Cutaneous PDT of IL-10 KO mice resulted in CHS suppression that was not significantly different from suppression induced in wild-type mice. Thus, it appears as though IL-10 does not play a role in CHS suppression by cutaneous PDT. Suppression of cell-mediated immune reactions by UVB and transdermal PDT is reversible by IL-12, which is critical for the development of these reactions. We show that administration of exogenous IL-12 is also able to reverse CHS suppression induced by cutaneous PDT, suggesting that whereas suppression of cell-mediated immune reactions by UVB, transdermal PDT and cutaneous PDT occurs via different mechanisms, a common regulatory point exists.
authors.affiliation: PDT Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. sandra.gollnick@roswellpark.org
authors.forename: S O
authors.initials: SO
authors.lastname: Gollnick
authors.forename: D A
authors.initials: DA
authors.lastname: Musser
authors.forename: A R
authors.initials: AR
authors.lastname: Oseroff
authors.forename: L
authors.initials: L
authors.lastname: Vaughan
authors.forename: B
authors.initials: B
authors.lastname: Owczarczak
authors.forename: B W
authors.initials: BW
authors.lastname: Henderson
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D017323:Dihematoporphyrin Ether / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018462:Photobiology; D010778:Photochemotherapy / Q000009:adverse effects*; D012867:Skin / Q000187:drug effects / Q000276:immunology
chemical_list: D016753:Interleukin-10; D018664:Interleukin-12; D017323:Dihematoporphyrin Ether