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Intrathecal Interferon in Multiple Sclerosis

Intrathecal Interferon in Multiple Sclerosis Abstract • Human fibroblast interferon (IFN-β) was administered by serial lumbar puncture to ten patients with multiple sclerosis (MS). Their clinical courses were compared with those of ten MS control patients who did not receive IFN-β. As of this writing, the recipients have been followed up for 1.8 to 2.0 years (mean, 1.9 years), and the controls for 1.5 to 1.7 years (mean, 1.6 years). During the study, two recipients suffered four exacerbations, and six controls suffered 11 exacerbations. The recipients' rates of exacerbation during the study were significantly less than their rates both for the entire prestudy duration of the disease and for the 1.8 to 2.0 years immediately preceding entry into the study. The controls' rates of exacerbation before the study and during the study period did not differ significantly. Clinically, the conditions of five recipients and two controls improved, those of three recipients and four controls were unchanged, and those of two recipients and four controls worsened. Headaches, sometimes accompanied by fever and rarely by nausea and vomiting, occurred after injections of IFN-β. Toxic symptoms usually disappeared within 24 hours; rarely, they persisted for seven to ten days. Each recipient had transient CSF pleocytosis and elevated levels of total protein (the latter remaining elevated in seven). These findings show that intrathecal administration of IFN-β is feasible in patients with MS, warrant cautious optimism that intrathecal IFN-β may be effective in altering the course of the disease, and support concepts of a viral or dysimmune cause of MS. References 1. Cook D, Dowling PC: Multiple sclerosis and viruses: An overview . Neurology 1980;20:80-91.Crossref 2. Johnson RT, Lazzarini RA, Waksman BH: Mechanism of virus persistence . Ann Neurol 1981;9:616-617.Crossref 3. Hitchcock G, Porterfield JS: The production of interferon in brains of mice infected with an arthroped-borne virus . Neurology 1961;13:363-365. 4. Wheelock EF: Applied and induced interferon in the prophylaxis and treatment of leukemia . Arch Intern Med 1970;126:64-68.Crossref 5. Jordan GW, Fried RP, Merigan TC: Administration of human leukocyte interferon in herpes zoster: I. Safety, circulating antiviral activity, and host responses to infection . J Infect Dis 1974;130:56-62.Crossref 6. Emodi G, Just M, Hernandez R, et al: Circulating interferon in man after administration of exogenous human leukocyte interferon . JNCI 1975;54:1045-1049. 7. Blomgren H, Cantell K, Johnasson B, et al: Interferon therapy in Hodgkin's disease . Acta Med Scand 1976;199:527-532.Crossref 8. Desmyter J, Ray MB, De Groute J, et al: Administration of human fibroblast interferon in chronic hepatitis B infection . Lancet 1976;2:654-657. 9. Greenberg HB, Pollard RB, Lutwick LI, et al: Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis . N Engl J Med 1976;295:517-522.Crossref 10. Larsson A, Forsgren J, Hard AF, et al: Administration of interferon to an infant with congenital rubella syndrome involving persistent viremia and cutaneous vasculitis . Acta Paediatr Scand 1976;65:105-110.Crossref 11. Strandler H, Cantell K, Carlstrom G, et al: Acute infections in interferon-treated patients with osteosarcoma: Preliminary report of a comparative study . J Infect Dis 1976;133 ( (suppl) ):A245-A248.Crossref 12. Hilfenhaus J, Weinman E, Major M, et al: Administration of human interferon to rabies virus-infected monkeys after exposure . J Infect Dis 1977;135:846-849.Crossref 13. Arvin A, Feldman S, Merigan TC: Human leukocyte interferon in the treatment of varicella in children with cancer: A preliminary controlled trial . Antimicrob Agents Chemother 1978;13:605-607.Crossref 14. Merigan TC, Rand KH, Pollard RB, et al: Human leukocyte interferon for the treatment of herpes zoster in patients with cancer . N Engl J Med 1978;298:981-987.Crossref 15. Dunnick JK, Galasso GJ: Clinical trials with exogenous interferon: Summary of a meeting . J Infect Dis 1979;139:109-123.Crossref 16. Pazin GJ, Armstrong JA, Lam MT, et al: Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root . N Engl J Med 1979;301:225-230.Crossref 17. Stewart WE II: The Interferon System . New York, Springer Verlag, 1979. 18. DeClercq E, Edy VG, DeVlieger H, et al: Intrathecal administration of interferon in neonatal herpes . J Pediatr 1975;86:736-739.Crossref 19. Habif DV, Lipton R, Cantell K: Interferon crosses blood-cerebrospinal fluid barrier in monkeys . Proc Soc Exp Biol Med 1975;149:287-298.Crossref 20. Hill NO, Loeb E, Pardu AS, et al: Response of acute leukemia to leukocyte interferon . J Clin Hematol Oncol 1979;9:137-150. 21. Misset JL, Mathe G, Horoszewicz JS: Intrathecal interferon in meningeal leukemia . N Engl J Med 1981;304:1544.Crossref 22. Salazar AM, Gibbs CJ, Gajusek CD, et al: Clinical use of interferons: Central nervous system disorders, in Came P, Carter W (eds): Handbook of Experimental Pharmacology. New York, Springer Verlag, in press. 23. Prange H, Wismann H: Intrathecal use of interferon in encephalitis . N Engl J Med 1981;305:1283-1284.Crossref 24. Jacobs L, O'Malley J, Freeman A, et al: Human fibroblast interferon (IFN-β) in multiple sclerosis , in 12th World Congress of Neurology, Kyoto, Japan . Amsterdam, Excerpta Medica, 1981. 25. Jacobs L, O'Malley J, Freeman A, et al: Intrathecal interferon reduces exacerbations of multiple sclerosis . Science 1981;214:1026-1028.Crossref 26. Jacobs L, O'Malley J, Freeman A, et al: Erratum . Science 1982;216:800.Crossref 27. Schumacher GA, Berbe G, Kibler RF, et al: Problems of experimental trials of therapy in multiple sclerosis: Report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis . Ann NY Acad Sci 1965;122:552-562.Crossref 28. McDonald WI: What is multiple sclerosis? Clinical criteria for diagnosis , in Davison AN, Humphrey JH, Liversedge LA, et al (eds): Multiple Sclerosis Research . New York, Elsevier North-Holland Inc, 1975, p 5. 29. Brown JR, Beebe GW, Kurtzke JR, et al: The design of clinical studies to assess therapeutic efficacy in multiple sclerosis : Neurology 1979;29:3-23.Crossref 30. Confavreux C, Aimard G, Devic M: Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients . Brain 1980;103:281-300.Crossref 31. Rose AS, Kuzma JW, Kurtzke JF, et al: Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs placebo in acute exacerbations, preliminary report . Neurology 1968;18:1-10. 32. Kurtzke JF: Further notes on disability evaluation in multiple sclerosis, with scale modifications . Neurology 1965;15:654-661.Crossref 33. Horoszewicz JS, Leong SS, Ito M, et al: Aging in vitro and large-scale interferon production by 15 new strains of human fibroblasts . Infect Immun 1978;19:720-726. 34. Horoszewicz JS, Leong SS, Ito M, et al: Human fibroblast interferon in human neoplasia: Clinical and laboratory study . Cancer Treat Rep 1978;62:1-8. 35. Finter NB: Dye uptake methods for assessing viral cytopathogenicity and their application to interferon assays . J Gen Virol 1969;5:419-427.Crossref 36. McAlpine D, Lumsden CE, Acheson ED: Multiple Sclerosis: A Reappraisal . Baltimore, Williams & Wilkins Co, 1972, p 205. 37. Burks JS, Macmillan BD, Jankorski L, et al: Characterization of coronaviruses isolated using multiple sclerosis brain material . Neurology 1979;29:547.Crossref 38. Rorke LB, Iwasaki Y, Koprowski H, et al: Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS . Ann Neurol 1979;5:89-94.Crossref 39. Wroblecka Z, Gilden D, Devlin M, et al: Cytomegalovirus isolation from a chimpanzee with acute demyelinating disease after inoculation of multiple sclerosis brain cells . Infect Immun 1979;25:1008-1034. 40. Detels R, Myers LW, Ellison GW, et al: Changes in immune response during relapses in MS patients . Neurology 1981;31:492-495.Crossref 41. Goust JM, Hoffman PM, Pryjma J, et al: Defective immunoregulation in multiple sclerosis . Ann Neurol 1980;8:526-533.Crossref 42. Aron R: Immunological approaches to control of multiple sclerosis , in Davison AN, Humphrey JH, Liversedge LA (eds): Multiple Sclerosis Research . New York, Elsevier North-Holland Inc, 1975, pp 271-290. 43. Borden EC: Interferons: Rationale for clinical trials in neoplastic disease . Arch Intern Med 1979;91:472-479. 44. Robertson M: Nerves, myelin and multiple sclerosis . Nature 1981;290:357-358.Crossref 45. Sumaya CV, Myers LW, Ellison GW: Epstein-Barr virus antibodies in multiple sclerosis . Arch Neurol 1980;37:94-96.Crossref 46. Haahr S: Virus inhibiting activity in the cerebro-spinal fluid from patients with acute and chronic neurological disorders . Acta Pathol Microbiol Scand 1971;79:606-608. 47. Degre M, Dahl H, Nadvik B: Interferon in the serum and cerebrospinal fluid in patients with multiple sclerosis and other neurological disorders . Acta Neurol Scand 1976;53:152-160.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Intrathecal Interferon in Multiple Sclerosis

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Publisher
American Medical Association
Copyright
Copyright © 1982 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1982.00510220007002
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Abstract

Abstract • Human fibroblast interferon (IFN-β) was administered by serial lumbar puncture to ten patients with multiple sclerosis (MS). Their clinical courses were compared with those of ten MS control patients who did not receive IFN-β. As of this writing, the recipients have been followed up for 1.8 to 2.0 years (mean, 1.9 years), and the controls for 1.5 to 1.7 years (mean, 1.6 years). During the study, two recipients suffered four exacerbations, and six controls suffered 11 exacerbations. The recipients' rates of exacerbation during the study were significantly less than their rates both for the entire prestudy duration of the disease and for the 1.8 to 2.0 years immediately preceding entry into the study. The controls' rates of exacerbation before the study and during the study period did not differ significantly. Clinically, the conditions of five recipients and two controls improved, those of three recipients and four controls were unchanged, and those of two recipients and four controls worsened. Headaches, sometimes accompanied by fever and rarely by nausea and vomiting, occurred after injections of IFN-β. Toxic symptoms usually disappeared within 24 hours; rarely, they persisted for seven to ten days. Each recipient had transient CSF pleocytosis and elevated levels of total protein (the latter remaining elevated in seven). These findings show that intrathecal administration of IFN-β is feasible in patients with MS, warrant cautious optimism that intrathecal IFN-β may be effective in altering the course of the disease, and support concepts of a viral or dysimmune cause of MS. References 1. Cook D, Dowling PC: Multiple sclerosis and viruses: An overview . Neurology 1980;20:80-91.Crossref 2. Johnson RT, Lazzarini RA, Waksman BH: Mechanism of virus persistence . Ann Neurol 1981;9:616-617.Crossref 3. Hitchcock G, Porterfield JS: The production of interferon in brains of mice infected with an arthroped-borne virus . Neurology 1961;13:363-365. 4. Wheelock EF: Applied and induced interferon in the prophylaxis and treatment of leukemia . Arch Intern Med 1970;126:64-68.Crossref 5. Jordan GW, Fried RP, Merigan TC: Administration of human leukocyte interferon in herpes zoster: I. Safety, circulating antiviral activity, and host responses to infection . J Infect Dis 1974;130:56-62.Crossref 6. Emodi G, Just M, Hernandez R, et al: Circulating interferon in man after administration of exogenous human leukocyte interferon . JNCI 1975;54:1045-1049. 7. Blomgren H, Cantell K, Johnasson B, et al: Interferon therapy in Hodgkin's disease . Acta Med Scand 1976;199:527-532.Crossref 8. Desmyter J, Ray MB, De Groute J, et al: Administration of human fibroblast interferon in chronic hepatitis B infection . Lancet 1976;2:654-657. 9. Greenberg HB, Pollard RB, Lutwick LI, et al: Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis . N Engl J Med 1976;295:517-522.Crossref 10. Larsson A, Forsgren J, Hard AF, et al: Administration of interferon to an infant with congenital rubella syndrome involving persistent viremia and cutaneous vasculitis . Acta Paediatr Scand 1976;65:105-110.Crossref 11. Strandler H, Cantell K, Carlstrom G, et al: Acute infections in interferon-treated patients with osteosarcoma: Preliminary report of a comparative study . J Infect Dis 1976;133 ( (suppl) ):A245-A248.Crossref 12. Hilfenhaus J, Weinman E, Major M, et al: Administration of human interferon to rabies virus-infected monkeys after exposure . J Infect Dis 1977;135:846-849.Crossref 13. Arvin A, Feldman S, Merigan TC: Human leukocyte interferon in the treatment of varicella in children with cancer: A preliminary controlled trial . Antimicrob Agents Chemother 1978;13:605-607.Crossref 14. Merigan TC, Rand KH, Pollard RB, et al: Human leukocyte interferon for the treatment of herpes zoster in patients with cancer . N Engl J Med 1978;298:981-987.Crossref 15. Dunnick JK, Galasso GJ: Clinical trials with exogenous interferon: Summary of a meeting . J Infect Dis 1979;139:109-123.Crossref 16. Pazin GJ, Armstrong JA, Lam MT, et al: Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root . N Engl J Med 1979;301:225-230.Crossref 17. Stewart WE II: The Interferon System . New York, Springer Verlag, 1979. 18. DeClercq E, Edy VG, DeVlieger H, et al: Intrathecal administration of interferon in neonatal herpes . J Pediatr 1975;86:736-739.Crossref 19. Habif DV, Lipton R, Cantell K: Interferon crosses blood-cerebrospinal fluid barrier in monkeys . Proc Soc Exp Biol Med 1975;149:287-298.Crossref 20. Hill NO, Loeb E, Pardu AS, et al: Response of acute leukemia to leukocyte interferon . J Clin Hematol Oncol 1979;9:137-150. 21. Misset JL, Mathe G, Horoszewicz JS: Intrathecal interferon in meningeal leukemia . N Engl J Med 1981;304:1544.Crossref 22. Salazar AM, Gibbs CJ, Gajusek CD, et al: Clinical use of interferons: Central nervous system disorders, in Came P, Carter W (eds): Handbook of Experimental Pharmacology. New York, Springer Verlag, in press. 23. Prange H, Wismann H: Intrathecal use of interferon in encephalitis . N Engl J Med 1981;305:1283-1284.Crossref 24. Jacobs L, O'Malley J, Freeman A, et al: Human fibroblast interferon (IFN-β) in multiple sclerosis , in 12th World Congress of Neurology, Kyoto, Japan . Amsterdam, Excerpta Medica, 1981. 25. Jacobs L, O'Malley J, Freeman A, et al: Intrathecal interferon reduces exacerbations of multiple sclerosis . Science 1981;214:1026-1028.Crossref 26. Jacobs L, O'Malley J, Freeman A, et al: Erratum . Science 1982;216:800.Crossref 27. Schumacher GA, Berbe G, Kibler RF, et al: Problems of experimental trials of therapy in multiple sclerosis: Report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis . Ann NY Acad Sci 1965;122:552-562.Crossref 28. McDonald WI: What is multiple sclerosis? Clinical criteria for diagnosis , in Davison AN, Humphrey JH, Liversedge LA, et al (eds): Multiple Sclerosis Research . New York, Elsevier North-Holland Inc, 1975, p 5. 29. Brown JR, Beebe GW, Kurtzke JR, et al: The design of clinical studies to assess therapeutic efficacy in multiple sclerosis : Neurology 1979;29:3-23.Crossref 30. Confavreux C, Aimard G, Devic M: Course and prognosis of multiple sclerosis assessed by the computerized data processing of 349 patients . Brain 1980;103:281-300.Crossref 31. Rose AS, Kuzma JW, Kurtzke JF, et al: Cooperative study in the evaluation of therapy in multiple sclerosis: ACTH vs placebo in acute exacerbations, preliminary report . Neurology 1968;18:1-10. 32. Kurtzke JF: Further notes on disability evaluation in multiple sclerosis, with scale modifications . Neurology 1965;15:654-661.Crossref 33. Horoszewicz JS, Leong SS, Ito M, et al: Aging in vitro and large-scale interferon production by 15 new strains of human fibroblasts . Infect Immun 1978;19:720-726. 34. Horoszewicz JS, Leong SS, Ito M, et al: Human fibroblast interferon in human neoplasia: Clinical and laboratory study . Cancer Treat Rep 1978;62:1-8. 35. Finter NB: Dye uptake methods for assessing viral cytopathogenicity and their application to interferon assays . J Gen Virol 1969;5:419-427.Crossref 36. McAlpine D, Lumsden CE, Acheson ED: Multiple Sclerosis: A Reappraisal . Baltimore, Williams & Wilkins Co, 1972, p 205. 37. Burks JS, Macmillan BD, Jankorski L, et al: Characterization of coronaviruses isolated using multiple sclerosis brain material . Neurology 1979;29:547.Crossref 38. Rorke LB, Iwasaki Y, Koprowski H, et al: Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS . Ann Neurol 1979;5:89-94.Crossref 39. Wroblecka Z, Gilden D, Devlin M, et al: Cytomegalovirus isolation from a chimpanzee with acute demyelinating disease after inoculation of multiple sclerosis brain cells . Infect Immun 1979;25:1008-1034. 40. Detels R, Myers LW, Ellison GW, et al: Changes in immune response during relapses in MS patients . Neurology 1981;31:492-495.Crossref 41. Goust JM, Hoffman PM, Pryjma J, et al: Defective immunoregulation in multiple sclerosis . Ann Neurol 1980;8:526-533.Crossref 42. Aron R: Immunological approaches to control of multiple sclerosis , in Davison AN, Humphrey JH, Liversedge LA (eds): Multiple Sclerosis Research . New York, Elsevier North-Holland Inc, 1975, pp 271-290. 43. Borden EC: Interferons: Rationale for clinical trials in neoplastic disease . Arch Intern Med 1979;91:472-479. 44. Robertson M: Nerves, myelin and multiple sclerosis . Nature 1981;290:357-358.Crossref 45. Sumaya CV, Myers LW, Ellison GW: Epstein-Barr virus antibodies in multiple sclerosis . Arch Neurol 1980;37:94-96.Crossref 46. Haahr S: Virus inhibiting activity in the cerebro-spinal fluid from patients with acute and chronic neurological disorders . Acta Pathol Microbiol Scand 1971;79:606-608. 47. Degre M, Dahl H, Nadvik B: Interferon in the serum and cerebrospinal fluid in patients with multiple sclerosis and other neurological disorders . Acta Neurol Scand 1976;53:152-160.Crossref

Journal

Archives of Neurology – American Medical Association

Published: Oct 1, 1982

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