Skip to main content
SpringerLink
Log in

Treatment of Multiple Sclerosis with Type I Interferons

  • Chapter
Multiple Sclerosis

Abstract

Interferons (IFNs) were first detected based on their antiviral properties (Isaacs and Lindenmann 1957), and classified as leukocyte, fibroblast or immune IFN, according to their cellular source. IFNs are now known to comprise a family of more than 20 different proteins, categorized as type I IFN (leukocyte and fibroblast IFN) and type II IFN (immune IFN). Current nomenclature (Table 11.1) is based on sequence analysis of the IFN genes. There are four distinct varieties of type I IFN (IFN-α, IFN-β, IFN-τ and IFN-ω) and a single type II IFN (IFN-γ). In humans, there are at least 18 non-allelic IFN-α genes, four of which are pseudogenes, at least six non-allelic IFN-ω genes, five of which are pseudogenes, but only a single IFN-β gene. Type I IFN genes lack introns and are located on the short arm of chromosome 9. IFN-γ is encoded by a single gene with three introns on chromosome 12. Trophoblast IFN (IFN-τ), a recently described IFN, functions to maintain the gravid state in pregnant female ruminants. IFN-τ has not yet been described in humans. It interacts with the IFN-α/β receptor, although its expression is regulated quite differently (Li and Roberts 1994).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aguet M, Dembic Z, Merlin G (1988) Molecular cloning and expression of the human IFN-gamma receptor. Cell 55: 273–280

    Article  PubMed  CAS  Google Scholar 

  • Allegretta M, Nicklas JA, Sriram S, Albertini RJ (1990) T cells responsive to myelin basic protein in patients with multiple sderosis. Science. 247: 718–721

    Article  PubMed  CAS  Google Scholar 

  • Antel JP, Arnason BGW, Medof ME (1979) Suppressor cell function in multiple sclerosis: correlation with clinical disease activity. Ann Neurol 5: 338–342

    Article  PubMed  CAS  Google Scholar 

  • AUSTIMS Research Group (1989) Interferon-alpha and transfer factor in the treatment of multiple sclerosis: a double-blind, placebo-controlled trial. J Neurol Neurosurg Psychiatry 52: 566–574

    Article  Google Scholar 

  • Barna BP, Chou SM, Jacobs B, Yen-Lieberman B, Ransohoff RM (1989) Interferon-beta impairs induction of HLA-DR antigen expression in cultured adult human astrocytes. J Neuroimmunol 23: 45–53

    Article  PubMed  CAS  Google Scholar 

  • Baron S, Tyiring SK, Fleischmann WR et al. (1991) The interferons, mechanisms of action and clinical applications. JAMA 266: 1375–1383

    Article  PubMed  CAS  Google Scholar 

  • Baron S, Coppenhaver DH, Dianzani F et al. (1992) Introduction to the interferon system. In: Baron S, Coppenhaver DH, Dianzani F et al. (eds) Interferon: principles and medical applications. The University of Texas Medical Branch Department of Microbiology, Galveston, TX, pp 1–15

    Google Scholar 

  • Bö L, Mork S, Kong PA, Nyland H, Pardo CA, Trapp BD (1994) Detection of MHC class II antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions. J Neuroimmunol 51: 135–146

    Article  PubMed  Google Scholar 

  • Borden EC (1992) Interferons: pleiotropic cellular modulators. Clin Immunol Immunopathol 62: 518–524

    Article  Google Scholar 

  • Borden E, Paulnock D, Spear G, Byrne G, Merrit J, Brown R (1986) Biological response modification in man: measurement of interferon induced proteins. In: Baron S, Dianzani F, Stanton JC, Fleischmann WR (eds) The interferon system: a current review. University of Texas Press, Austin, TX, pp 1–7

    Google Scholar 

  • Camenga DL, Johnson KP, Alter M et al. (1986) Systemic recombinant alpha-2 interferon therapy in relapsing multiple sclerosis. Arch Neurol 43: 1239–1246

    PubMed  CAS  Google Scholar 

  • Darnell JE, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264: 1415–1421

    Article  PubMed  CAS  Google Scholar 

  • Durelli L, Poccardi G, Cavallo R (1991) CD8+ high CD11b+ low T cells ( T suppressor-effectors) in multiple sclerosis cerebrospinal fluid are increased during high dose corticosteroid treatment. J Neuroimmunol 31: 221–228

    Article  PubMed  CAS  Google Scholar 

  • Durelli L, Bongioanni MR, Cavallo R et al. (1994) Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis. Neurology 44: 406–413

    PubMed  CAS  Google Scholar 

  • Fog T (1980) Interferon treatment of multiple sclerosis patients. A pilot study. In: Boese A (ed) Search for the cuase of MS and other chronic diseases of the CNS. Weinheim, Verlag Chemie, pp 490–493

    Google Scholar 

  • Friedman WH, Gresser I, Bandeu MT, Aguet M, Neauport-Sautes C (1980) Interferon enhances the expression of Fc gamma receptors. J Immunol 124: 2436–2441

    Google Scholar 

  • Gauci L (1987) Management of cancer patients receiving interferon alfa-2a. Int J Cancer 1 Supp1: 21–30

    Google Scholar 

  • Gibbs CJ, Gajdusek DC, Alpers MP (1969) Attempts to transmit subacute and chronic neurological diseases to animals. In: Burdzy K, Kallos P (eds) Pathogenesis and etiology of demyelinating diseases. Karger, Basel, pp 519–552

    Google Scholar 

  • Hemmi S, Bohni R, Stark G, DiMarco F, Aguet M (1994) A novel member of the interferon receptor family complements functionality of the murine interferon gamma receptor. Cell 76: 803–810

    Article  PubMed  CAS  Google Scholar 

  • IFNB Multiple Sclerosis Study Group (1993) Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43: 655–661

    Google Scholar 

  • IFNB Multiple Sderosis Study Group and the University of British Columbia MS/MRI Analysis Group (1995). Interferon beta-lb in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 45: 1277–1285

    Google Scholar 

  • Isaac A, Lindenmann J (1957) Virus interference: I. The interferon. Proc R Soc Land B Biol Sei 147: 258–267

    Article  Google Scholar 

  • Jacobs L, O’Malley J, Freeman A, Ekes R (1981) Intrathecal interferon reduces exacerbations of multiple sclerosis. Science 214: 1026–1028

    Article  PubMed  CAS  Google Scholar 

  • Jacobs L, Salazar AM, Herndon R, Reese PA, Freeman A et al. (1986) Multicentre double-blind study of effect of intrathecally administered natural human fibroblast interferon on exacerbations of multiple sclerosis. Lancet iî: 1411–1413

    Article  Google Scholar 

  • Jacobs L, Munschauer F (1992) Treatment of multiple sclerosis with interferons. In: Rudick R, Goodkin D (eds) Treatment of multiple sclerosis. Springer-Verlag, London, pp 233–250

    Google Scholar 

  • Jacobs L, Cookfair D, Rudick R et al. (1996) Intramuscular interferon beta-1-a for disease progression in relapsing multiple sclerosis. Ann Neurol 39: 285–294

    Article  PubMed  CAS  Google Scholar 

  • Johnson HM, Bazer FW, Szente BE, Jarpe RA (1994) How interferons fight disease. Sci Am 5:40–47

    Google Scholar 

  • Johnson KP, Knobler RL, Greenstein JI et al. (1990) Recombinant human interferon beta treatment of relapsing-remitting multiple sclerosis: pilot study results [abstract]. Neurology 40(Suppl. 1):26

    Google Scholar 

  • Kastrukoff LF, Oger JJ, Hashimoto SA et al. (1990) Systemic lymphoblastoid interferon therapy in chronic progressive multiple sclerosis: I. Clinical and MRI evaluation. Neurology 40: 479–486

    PubMed  CAS  Google Scholar 

  • Knobler KP, Greenstein JI, Johnson KP et al. (1993) Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sderosis: pilot study analysis and six-year follow-up. j Interferon Res 13: 333–340

    CAS  Google Scholar 

  • Knobler RL, Panitch HS, Braheny SL et al. (1984) Systemic alpha-interferon therapy of multiple sclerosis. Neurology 34: 1273–1279

    PubMed  CAS  Google Scholar 

  • Koopmans RA, Li DKB, Oger JJF, Mayo J, Paty DW (1989) The lesion of multiple sclerosis: imaging of acute and chronic stages. Neurology 39: 959–963

    PubMed  CAS  Google Scholar 

  • Krown SE (1987) Clinical trials of interferons in human malignancy. In: Pfeffer LM (ed) Mechanisms of interferon actions, vol. II. CRC Press, Boca Raton, FL, pp 144–178

    Google Scholar 

  • Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33: 1444–1452

    PubMed  CAS  Google Scholar 

  • Lengyel P (1982) Biochemistry of interferons and their actions. Ann Rev Biochem 51: 251–282

    Article  PubMed  CAS  Google Scholar 

  • Li J, Roberts RM (1994) Interferon-tau and interferon-alpha interact with the same receptors in bovine endometrium. Use of a readily iodinatable form of recombinant interferon-tau forbinding studies. J Biol Chem 269: 13544–13550

    CAS  Google Scholar 

  • Ling PD, Warren MK, Vogel SN (1985) Antagonistic effect of interferon-beta on the interferon-gamma-induced expression of la antigen in murine macrophages. J Immunol 135: 1857–1863

    PubMed  CAS  Google Scholar 

  • McFarland HF, Frank JA, Albert PS et al. (1992) Using gadolinium-enhanced magnetic resonanceimaging lesions to monitor disease activity in multiple sclerosis. Ann Neurol 32: 758–766

    Article  PubMed  CAS  Google Scholar 

  • Melamed D, Tietenbrun N, Yarden A, Kimchi A (1993) Interferons and interleukin-6 suppress the DNA-binding activity of E2F in growth-sensitive hematopoietic cells. Mol Cell Biol 13: 5255–5265

    PubMed  CAS  Google Scholar 

  • Miller DH, Barkhof F, Berry I, Kappos L, Scotti G, Thompson AJ (1991) Magnetic resonance imaging in monitoring the treatment of multiple sclerosis: concerted action guidelines. J Neurol Neurosurg Psychiatry 54: 683–688

    Article  PubMed  CAS  Google Scholar 

  • Muller M, Briscoe J, Laxton C et al. (1993) The protein tyrosine kinase JAK 1 complements defects in interferon alpha/beta and gamma signal transduction. Nature 366: 129–135

    Article  PubMed  CAS  Google Scholar 

  • Multiple Sclerosis Study Group (1990) Efficacy and toxicity of cyclosporin in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. Ann Neurol 27: 591–605

    Article  Google Scholar 

  • Nauta JJP, Barkhof F, Thompson AJ, Miller DH (1994) Magnetic resonance imaging in monitoring the treatment of multiple sderosis patients: statistical power of parallel-groups and crossover designs. J Neurol Sci 122: 6–14

    Article  PubMed  CAS  Google Scholar 

  • Noronha A, Toscas A, Jensen MA (1990) Interferon beta augments suppressor cell function in multiple sclerosis. Ann Neurol 27: 207–210

    Article  PubMed  CAS  Google Scholar 

  • Noronha A, Toscas A, Jensen MA (1991) IFN-beta down-regulates IFN-gamma production by activated T cells in MS [abstract]. Neurology 41 (Suppl 1): 219

    Google Scholar 

  • Noronha A, Toscas A, Jensen MA (1992) Contrasting effects of alpha, beta and gamma interferons on nonspecific suppression function in multiple sclerosis. Ann Neurol 31: 103–106

    Article  PubMed  CAS  Google Scholar 

  • Noronha A, Toscas A, Jensen MA (1993) Interferon 43 decreases T cell activation and interferon y production in multiple sclerosis. J Neuroimmunol 46: 145–154

    Article  PubMed  CAS  Google Scholar 

  • Novick D, Cohen B, Rubinstein M (1994) The human interferon alpha/beta receptor: characterization and molecular cloning. Cell 77: 391–400

    Article  PubMed  CAS  Google Scholar 

  • Olsson T, Sun J, Hillert J et al. (1992) Increased numbers of T cells recognizing multiple myelin basic protein epitopes in multiple sclerosis. Eur J Immunol 22: 1083–1087

    Article  PubMed  CAS  Google Scholar 

  • Panitch HS (1994) Influence of infection on exacerbations of multiple sclerosis. Ann Neurol 36 (Suppl 1): S25 - S28

    Article  PubMed  Google Scholar 

  • Paty DW, Li DKB, the UBC MS/MRI Study Group, and the IFNB Multiple Sclerosis Study Group (1993) Interferon beta-lb is effective in relapsing-remitting multiple sclerosis: II. MM analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43: 662–667

    Google Scholar 

  • Pestka S, Langer JA, Zoon KC, Samuel CE. (1987) Interferons and their actions. Annu Rev Biochem 56: 727–777

    Article  PubMed  CAS  Google Scholar 

  • Platanias LC, Golomb HM (1992) Clinical use of interferons: hairy cell, chronic myelogenous and other leukemias. In: Baron S, Coppenhaver DH, Dianzani F et al. (eds) Interferon: principles and medical applications. University of Texas Medical Branch Department of Microbiology, Galveston, TX, pp 487–499

    Google Scholar 

  • Quesada JR (1992) Toxicity and side effects of interferons. In: Baron S, Coppenhaver DH, Dianzani F et al. (eds) Interferon: principles and medical applications. University of Texas Medical Branch Department of Microbiology, Galveston, TX, pp 427–432

    Google Scholar 

  • Ransohoff RM, Devajyothi C, Estes ML et al. (1991) Interferon-43 specifically inhibits interferon-y induced class II major histocompatibility complex gene transcription in a human astrocytoma cell line. J Neuroimmunol 33: 103–112

    Article  PubMed  CAS  Google Scholar 

  • Ransohoff RM, Tuohy VK, Barna BP, Rudick RA (1992) Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vivo. J Neuroimmunol 37: 169–176

    Article  PubMed  CAS  Google Scholar 

  • Rudick RA, Carpenter CS, Cookfair DL, Tuohy VK, Ransohoff RM (1993) In vitro and in vivo inhibition of mitogen-driven T-cell activation by recombinant interferon beta. Neurology 43: 2080–2087

    PubMed  CAS  Google Scholar 

  • Saracco G, Rosina F, Abate ML et al. (1993) Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon alpha-2b. Hepatology 18: 1300–1305

    Article  PubMed  CAS  Google Scholar 

  • Sekar V, Atmar VJ, Joshi AR, Krim M, Kuehn G (1983) Inhibition of ornithine decarboylase in human fibroblast cells by type I and type II interferons. Biochem Biophys Res Commun 114: 950–954

    Article  PubMed  CAS  Google Scholar 

  • Selmaj K, Brosnan CF, Raine CS (1991) Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci USA 88: 6452–6456

    Article  PubMed  CAS  Google Scholar 

  • Sen GC, Lengyel P (1992) The interferon system: a bird’s eye view of its biochemistry. J Biol Chem 267: 5017–5020

    PubMed  CAS  Google Scholar 

  • Shearer M, Taylor-Papadimitriou J (1987) Regulation of cell growth by interferon. Cancer Metast Rev 6: 199–221

    Article  CAS  Google Scholar 

  • Shuai K, Ziemiecki A, Wilks AF et al. (1993) Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat protein. Nature 366: 580–583

    Article  PubMed  CAS  Google Scholar 

  • Shuai K, Horvath CM, Huang T, Gureshi SA, Cowburn D, Darnell JE (1994) Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell 76: 821–828

    Article  PubMed  CAS  Google Scholar 

  • Sibley WA, Tourtellotte WW (1968) Interferon assay of multiple sclerosis tissue. Trans Am Neurol Assoc 93: 124–126

    PubMed  CAS  Google Scholar 

  • Sibley WA, Laguna JF, Kalter SS (1980) Attempts to transmit multiple sclerosis to newborn and germ-free non-human primates: a ten-year interim report. In: Bauer HJ, Poser S, Ritter G (eds) Progress in multiple sclerosis research. Springer-Verlag, Berlin, pp 80–85

    Google Scholar 

  • Sibley WA, Bamford CR, Clark K (1985) Clinical viral infections and multiple sclerosis. Lancet i: 1313–1315

    Article  Google Scholar 

  • Sipe JC, Knobler RL, Braheny SL, Rice GPA, Panitch HS, Oldstone MBA (1984) A neurologic rating scale ( NRS) for use in multiple sclerosis. Neurology 34: 1368–1372

    PubMed  CAS  Google Scholar 

  • Soderstrom M, Link H, Sun JB et al. (1993) T cells recognizing multiple peptides of myelin basic protein are found in blood and enriched in cerebrospinal fluid in optic neuritis and multiple sclerosis. Scand J Immunol 37: 355–368

    Article  PubMed  CAS  Google Scholar 

  • Soh J, Donnelly RJ, Kotenko S et al. (1994) Identification and sequence of an accessory factor required for activation of the human interferon gamma receptor. Cell 76: 793–802

    Article  PubMed  CAS  Google Scholar 

  • Tominaga SI, Lengyel P (1985) Beta-interferon alters the pattern of proteins secreted from quiescentand platelet-derived growth factor-treated BALB/C-3T3 cells. J Biol Chem 260: 1975–1978

    PubMed  CAS  Google Scholar 

  • Traugott U, Reinherz EL, Raine CS (1983) Multiple sclerosis: distribution of T cells. T-cell subsetsand Ia-positive macrophages in lesions of different ages. J Immunol 4. 201–221

    CAS  Google Scholar 

  • Tyring SK (1992) Introduction to clinical uses of interferons. In: Baron S, Coppenhaver DH, Dianzani F et al. (eds) Interferon: principles and medical applications. University of Texas Medical Branch Department of Microbiology, Galveston, TX, pp 399–408

    Google Scholar 

  • Vilcek J, Sen GC (1995) Interferons and other cytokines. In: Fields BN, Knipe DM, Howley PM (eds) Fields’ virology. Raven Press, New York.

    Google Scholar 

  • Watling D, Guschin D, Muller M et al. (1993) Complementation by the protein tyrosine kinase Jak 2 of a mutant cell line defective in the interferon-gamma signal transduction pathway. Nature 366: 166 – 170.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Richard A. Rudick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William Sibley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luca Durelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The UCSF/Mount Zion Multiple Sclerosis Center, University of California at San Francisco, 1600 Divisadero Street, 94115, San Francisco, CA, USA

    Donald E. Goodkin MD

  2. Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195-5244, Cleveland, OH, USA

    Richard A. Rudick MD

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag London Limited

About this chapter

Cite this chapter

Rudick, R.A., Sibley, W., Durelli, L. (1996). Treatment of Multiple Sclerosis with Type I Interferons. In: Goodkin, D.E., Rudick, R.A. (eds) Multiple Sclerosis. Springer, London. https://doi.org/10.1007/978-1-4471-1271-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-1271-6_11

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-85233-033-0

  • Online ISBN: 978-1-4471-1271-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation