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Departments of Molecular Medicine [S. O. G.], Radiation Biology [B. O., X. L., B. W. H.], and Dermatology [D. A. M.], Roswell Park Cancer Institute, Buffalo, New York 14263
Photodynamic therapy (PDT), which can effectively destroy malignant tissue, also induces a complex immune response that potentiates antitumor immunity but also inhibits skin contact hypersensitivity (CHS) and prolongs skin graft survival. The underlying mechanisms responsible for these effects are poorly understood but are likely to involve mediation by cytokines. We demonstrate in a BALB/c mouse model that PDT delivered to normal and tumor tissue in vivo causes marked changes in the expression of cytokines interleukin (IL)-6 and IL-10 but not tumor necrosis factor
. IL-6 mRNA and protein are strongly enhanced in the PDT-treated EMT6 tumor. PDT also increased IL-6 mRNA in exposed spleen and skin. These data suggest that the general inflammatory response to PDT may be mediated at least in part by IL-6. In addition, IL-6 may modulate the local antitumor immune response. In contrast, IL-10 mRNA in the tumor decreases following PDT. Most importantly, IL-10 is markedly induced in the skin of mice exposed to a PDT regime that strongly inhibits the CHS response, and the kinetics of IL-10 induction coincide with the known kinetics of CHS inhibition. We propose that the enhanced IL-10 expression plays a role in the observed suppression of cell-mediated responses seen following PDT.
1 This work was supported by NIH Grant CA55791b (to B. W. H.). S. O. G. was partially supported by NIH Grant HD17013 and a grant from the Elisabeth and Peter Tower Foundation. D. A. M. was supported by NIH Grant CA55791c.
2 To whom requests for reprints should be addressed, at Department of Radiation Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263.
Received 7/ 2/97. Accepted 7/29/97.
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