Research Article| Volume 38, ISSUE 3, P189-195, June 2005

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Treatment with IFN-γ increases serum levels of Th1 chemokines and decreases those of Th2 chemokines in patients with mycosis fungoides



      Interferon-γ (IFN-γ) is used for the treatment of mycosis fungoides, which is a Th2 neoplasm with elevation of serum Th2 chemokines. Although therapeutic effectiveness of IFN-γ is caused at least partly by augmented activity of cytotoxic T cells against the tumor cells, its modulation on chemokine production remains unknown.


      Alterations in the serum levels of Th1 chemokines, IP-10 and MIG, and Th2 chemokines, TARC and MDC, were examined in mycosis fungoides patients treated with recombinant IFN-γ.


      Four patients with mycosis fungoides received intravenous injections of IFN-γ for 14 or 28 days. On day 0, 7, 14, and 28, sera were obtained from the patients, and the concentrations of TARC, MDC, IP-10, and MIG were measured by ELISA, along with the percentages of peripheral blood Th1 and Th2 cells.


      Whereas the levels of TARC and MDC were decreased by IFN-γ treatment, those of IP-10 and MIG were increased. In particular, the increment of MIG was remarkable. No substantial change of Th1 or Th2 cell number was observed.


      In IFN-γ treatment as well as other therapies, TARC may serve as a marker for the disease activity of mycosis fungoides. The dramatic elevation of MIG by IFN-γ suggests the strong dependency of MIG production on IFN-γ and the participation of MIG in skin-infiltration of tumoricidal cytotoxic T cells.


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        • Willemze R.
        • Kerl H.
        • Sterry W.
        • et al.
        EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer.
        Blood. 1997; 90: 354-371
        • Vowels B.R.
        • Lessin S.R.
        • Cassin M.
        • Jaworsky C.
        • Benoit B.
        • Wolfe J.T.
        • et al.
        Th2 cytokine mRNA expression in skin in cutaneous T cell lymphoma.
        J Invest Dermatol. 1994; 103: 669-673
        • Noorduyn L.A.
        • Beljaards R.C.
        • Pals S.T.
        • et al.
        Differential expression of the HECA-452 antigen (cutaneous lymphocyte-associated antigen, CLA) in cutaneous and non-cutaneous T-cell lymphomas.
        Histopathology. 1992; 21: 59-64
        • Berger C.L.
        • Wang N.
        • Christensen I.
        • Longley J.
        • Heald P.
        • Edelson R.L.
        The immune response to class I-associated tumor-specific cutaneous T-cell lymphoma antigens.
        J Invest Dermatol. 1996; 107: 392-397
        • Seo N.
        • Tokura Y.
        • Matsumoto K.
        • Furukawa F.
        • Takigawa M.
        Tumour-specific cytotoxic T lymphocyte activity in Th2-type Sézary syndrome: its enhancement by interferon-γ (IFN-γ) and IL-12 and fluctuations in association with disease activity.
        Clin Exp Immunol. 1998; 112: 403-409
        • Ishihara K.
        • Ikeda S.
        • Mori S.
        • Urabe H.
        • Arao R.
        Phase II study of recombinant human interferon γ (SUN4800) for cutaneous malignancies.
        Nishinihon Hifuka. 1989; 51: 766-775
        • Kaplan E.H.
        • Rosen S.T.
        • Norris D.B.
        • Roenigk Jr., H.H.
        • Saks S.R.
        • Bunn Jr., P.A.
        Phase II study of recombinant human interferon γ for treatment of cutaneous T-cell lymphoma.
        J Natl Cancer Inst. 1990; 82: 208-212
        • Rossi D.
        • Zlotnic A.
        The biology of chemokines and their receptors.
        Annu Rev Immunol. 2000; 18: 217-242
        • Kobayashi M.
        • Shimauchi T.
        • Hino R.
        • Tokura Y.
        Roxithromycin downmodulates Th2 chemokine production by keratinocytes and chemokine receptor expression on Th2 cells: its dual inhibitory effects on the ligands and the receptors.
        Cell Immunol. 2004; 228: 27-33
        • Sallusto F.
        • Lenig D.
        • Mackay C.R.
        • Lanzavecchia A.
        Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.
        J Exp Med. 1998; 187: 875-883
        • Ferenczi K.
        • Fuhlbrigge R.C.
        • Pinkus J.
        • Pinkus G.S.
        • Kupper T.S.
        Increased CCR4 expression in cutaneous T cell lymphoma.
        J Invest Dermatol. 2002; 19: 1405-1410
        • Kakinuma T.
        • Sugaya M.
        • Nakamura K.
        • Kaneko F.
        • Wakugawa M.
        • Matsushima K.
        • et al.
        Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides.
        J Am Acad Dermatol. 2003; 48: 23-30
        • Papadavid E.
        • Economidou J.
        • Psarra A.
        • Kapsimali V.
        • Mantzana V.
        • Antoniou C.
        • et al.
        The relevance of peripheral blood T-helper 1 and 2 cytokine pattern in the evaluation of patients with mycosis fungoides and Sézary syndrome.
        Br J Dermatol. 2003; 148: 709-718
        • Sanches J.L.
        • Ackerman A.B.
        The patch stage of mycosis fungoides.
        Am J Dermatopathol. 1979; 1: 5-26
        • Shapiro P.E.
        • Pinto F.J.
        The histollogic spectrum of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma). A review of 222 biopsies, including newly described patterns and the earliest pathologic changes.
        Am J Surg Pathol. 1994; 18: 645-667
        • Ikuta K.
        • Ogura T.
        • Shimizu A.
        • Honjo T.
        Low frequency of somatic mutation in beta-chain variable region genes of human T-cell receptors.
        Proc Natl Acad Sci USA. 1985; 82: 7701-7705
        • Yagi H.
        • Tokura Y.
        • Furukawa F.
        • Takigawa M.
        CD7-positive Sézary syndrome with a Th1 cytokine profile.
        J Am Acad Dermatol. 1996; 34: 368-374
        • Tsuda T.
        • Tohyama M.
        • Yamasaki K.
        • Shirakata Y.
        • Yahata Y.
        • Tokumaru S.
        • et al.
        Lack of evidence for TARC/CCL17 production by normal human keratinocytes in vitro.
        J Dermatol Sci. 2003; 31: 37-42
        • Kakinuma T.
        • Nakamura K.
        • Wakugawa M.
        • Yano S.
        • Saeki H.
        • Torii H.
        • et al.
        IL-4, but not IL-13, modulates TARC (thymus and activation-regulated chemokine)/CCL17 and IP-10 (interferon-induced protein of 10 kDA)/CXCL10 release by TNF-α and IFN-γ in HaCaT cell line.
        Cytokine. 2002; 20: 1-6
        • Xiao T.
        • Kagami S.
        • Saeki H.
        • Sugaya M.
        • Kakinuma T.
        • Fujita H.
        • et al.
        Both IL-4 and IL-13 inhibit the TNF-alpha and IFN-gamma enhanced MDC production in a human keratinocyte cell line, HaCaT cells.
        J Dermatol Sci. 2003; 31: 111-117
        • Mahalingam S.
        • Chaudhri G.
        • Tan C.L.
        • John A.
        • Foster P.S.
        • Karupiah G.
        Transcription of the interferon γ (IFN-γ)-inducible chemokine Mig in IFN-γ-deficient mice.
        J Biol Chem. 2001; 276: 7568-7574
        • Villagomez M.T.
        • Bae S.J.
        • Ogawa I.
        • Takenaka M.
        • Katayama I.
        Tumour necrosis factor-α but not interferon-γ is the main inducer of inducible protein-10 in skin fibroblasts from patients with atopic dermatitis.
        Br J Dermatol. 2004; 150: 910-916