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 tumor stage mycosis fungoides (MF), whereas its mechanism is still unknown. We have previously shown that treatment with intralesional IFN-gamma induced tumor regression.

OBJECTIVE

To explore the possibility that IFN-gamma may alter the cytokine expression by tumor cells, we studied cytokine gene expression in a tumor nodule of MF.

METHODS

By using the reverse transcriptase-polymerase chain reaction, Th1- and Th2-type cytokine mRNA expression was examined before and after intralesional IFN-gamma therapy. Additionally, we examined bel-2 protein expression on tumor cells.

RESULTS

We found weak mRNA expression of interleukin-4 (IL-4) and IL-5, and strong expression of IL-6, IL-10 and IFN-gamma before therapy. After successful treatment of intralesional IFN-gamma, 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 successful intralesional IFN-gamma therapy, photochemotherapy (PUVA) and radiation therapy.

CONCLUSION

These data suggest that IFN-gamma induces tumor regression by affecting cytokine gene expression in MF tumor lesions. The reduced bcl-2 expression did not seem to be induced by a direct immunological affect of IFN-gamma, but to represent a nonspecific result of tumor regression after successful treatment.