ALTERATION OF CYTOKINE GENES AND BCL-2 EXPRESSION FOLLOWING IMMUNOTHERAPY WITH INTRALESIONAL IFN-GAMMA IN A PATIENT WITH TUMOR-STAGE MYCOSIS-FUNGOIDES

Background: Interferon-gamma (IFN-gamma) is used in the treatment of t umor stage my cosis fungoides (MF), whereas its mechanism is still unk nown. We have previously shown that treatment with intralesional IFN-g amma induced tumor regression. Objective: To explore the possibility t hat IFN-gamma may alter the cytokine expression by tumor cells, we stu died cytokine gene expression in a tumor nodule of ME Methods: By usin g the reverse transcriptase-polymerase chain reaction, Th1- and Th2-ty pe cytokine mRNA expression was examined before and after intralesiona l IFN-gamma therapy. Additionally, we examined bcl-2 protein expressio n on tumor cells. Results: We found weak mRNA expression of interleuki n-4 (IL-4) and IL-5, and strong expression of IL-6, IL-10 and IFN-gamm a before therapy. After successful treatment of intralesional IFN-gamm a, mRNA expression of IL-5, IL-6 and IL-10 were significantly reduced and IL-2 mRNA was mildly induced. Culture for 24 h of tumor cells with IFN-gamma showed upregulation of IL-2 mRNA and downregulation of IL-6 mRNA expression. bcl-2 expression was significantly decreased after s uccessful intralesional IFN-gamma therapy, photochemotherapy (PUVA) an d radiation therapy. Conclusion: These data suggest that IFN-gamma ind uces tumor regression by affecting cytokine gene expression in MF tumo r lesions. The reduced bcl-2 expression did not seem to be induced by a direct immunological affect of IFN-gamma but to represent a nonspeci fic result of tumor regression after successful treatment.