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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Dermatological Science
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- 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
- Th2 cytokine mRNA expression in skin in cutaneous T cell lymphoma.J Invest Dermatol. 1994; 103: 669-673
- 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
- The immune response to class I-associated tumor-specific cutaneous T-cell lymphoma antigens.J Invest Dermatol. 1996; 107: 392-397
- 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
- Phase II study of recombinant human interferon γ (SUN4800) for cutaneous malignancies.Nishinihon Hifuka. 1989; 51: 766-775
- Phase II study of recombinant human interferon γ for treatment of cutaneous T-cell lymphoma.J Natl Cancer Inst. 1990; 82: 208-212
- The biology of chemokines and their receptors.Annu Rev Immunol. 2000; 18: 217-242
- 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
- Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.J Exp Med. 1998; 187: 875-883
- Increased CCR4 expression in cutaneous T cell lymphoma.J Invest Dermatol. 2002; 19: 1405-1410
- 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
- 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
- The patch stage of mycosis fungoides.Am J Dermatopathol. 1979; 1: 5-26
- 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
- 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
- CD7-positive Sézary syndrome with a Th1 cytokine profile.J Am Acad Dermatol. 1996; 34: 368-374
- Lack of evidence for TARC/CCL17 production by normal human keratinocytes in vitro.J Dermatol Sci. 2003; 31: 37-42
- 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
- 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
- Transcription of the interferon γ (IFN-γ)-inducible chemokine Mig in IFN-γ-deficient mice.J Biol Chem. 2001; 276: 7568-7574
- 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
Accepted: January 19, 2005
Received in revised form: January 4, 2005
Received: September 1, 2004
© 2005 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.