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.


CONCLUSIONS
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.
Yamamoto
T
T
Department of Dermatology, Tokyo Medical and Dental University School of Medicine, Japan.
Takahashi
Y
Y
Katayama
I
I
Nishioka
K
K
D016207:Cytokines / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D017931:DNA Primers; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015552:Injections, Intralesional; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D015854:Up-Regulation
D016207:Cytokines; D017931:DNA Primers; D016898:Interferon-alpha; D007376:Interleukin-2; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2