Research Article| Volume 78, ISSUE 1, P35-50, March 1987

Cyclosporine enhances virally induced T-cell-mediated demyelination

The effect of cyclosporine on a demyelinating virus infection
      This paper is only available as a PDF. To read, Please Download here.


      Semliki Forest virus infection of adult mice results in a demyelinating meningoencephalomyelitis. Demyelination does not result from direct viral damage but from the activity of T lymphocytes. We have studied the effect of the immunosuppressant cyclosporine (Cs) on the outcome of this infection. Cs had no effect when given 5 days after the infection, and little effect when given 4 h after infection. When the Cs was given 48 h before infection there was a prolongation of the blood and brain virus titres, and a reduction in some mice of serum IgG anti-viral antibody synthesis, but an increase in the severity of the CNS inflammatory response and the demyelination. Consideration of these findings along with measurement of Cs levels in the serum and cerebrospinal fluid suggests that this drug does not cross the blood brain barrier.


      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 to Journal of the Neurological Sciences
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Altmann D.W.
        • Blyth A.
        The effects of cyclosporine A on the induction expression and regulation of the immune response to herpes simplex virus.
        Clin. Exp. Immunol. 1985; 59: 17-22
        • Berger M.L.
        Humoral and cell mediated immune mechanisms in the production of pathology in avirulent Semliki Forest virus encephalitis.
        Infect. Immunol. 1980; 30: 244-253
        • Bolton C.
        • Allsopp G.
        • Cuzner M.L.
        The effect of cyclosporin A on the adoptive transfer of experimental allergic encephalomyelitis in the Lewis rat.
        Clin. Exp. Immunol. 1982; 47: 127-132
        • Borel J.F.
        • Wiesinger D.
        Effect of cyclosporin A on murine lymphoid cells.
        in: Lucas D.O. Regulatory Mechanisms on lymphocytes Activation. Academic Press, New York1977: 716
        • Borel J.F.
        • Feurer C.
        • Gubler H.U.
        • Stahelin H.
        Biological effects of cyclosporin A: A new antilymphocytic agent.
        Agents and Actions. 1976; 6: 468-475
        • Bradish C.J.
        • Allner K.
        • Maber H.B.
        The virulence of original and derived strains of Semliki Forest virus for mice, guinea-pigs and rabbits.
        J. Gen. Virol. 1971; 12: 141-160
        • Bruton C.J.
        • Kennedy S.I.T.
        Defective interfering particles of Semliki Forest virus: structural differences between standard virus and defective interfering particles.
        J. Gen. Virol. 1976; 31: 383-395
        • Carp R.I.
        • Davison A.I.
        • Herz P.A.
        A method for obtaining CSF from mice.
        Res. Vet. Sci. 1971; 12: 499
        • Donatsch P.
        A radioimmunoassay to measure cyclosporin A in plasma and serum samples.
        J. Immunoassay. 1981; 2: 19-32
        • Fazakerley J.K.
        • Amor S.
        • Webb H.E.
        Reconstitution of Semliki Forest virus infected mice, induces immune mediated pathological changes in the CNS.
        Clin. Exp. Immunol. 1983; 52: 115-120
        • Fazakerley J.K.
        • Webb H.E.
        Semliki Forest virus induced, immune mediated demyelination - Adoptive transfer studies and viral persistence in nude mice.
        J. Gen. Virol. 1986; (In press)
        • Fazakerley J.K.
        • Webb H.E.
        Semliki Forest virus induced, immune mediated demyelination.
        Brit. J. Exp. Path. 1986; (In press)
        • Fredane L.M.
        • Hashim G.A.
        • McCabe R.E.
        The effect of cyclosporine on lymphocyte subsets in experimental allergic encephalomyelitis: Functional loss of disease-suppressing cells in vivo.
        in: Transplant. Proc.15. 1983: 2909-2913 (Suppl. 1)
        • Illavia S.J.
        • Webb H.E.
        • Pathak S.
        Demyelination induced in mice by avirulent Semliki Forest virus, Part 1 (Effects on optic nerve).
        Neuropath. Appl. Neurobiol. 1982; 8: 35-42
        • Jagelman S.
        • Suckling A.J.
        • Webb H.E.
        • Bowen E.T.W.
        The pathogenesis of avirulent Semliki Forest virus infections in athymic nude mice.
        J. Gen. Virol. 1978; 41: 599-607
        • Kelly W.R.
        • Blakemore W.F.
        • Jagelman S.
        • Webb H.E.
        Demyelination induced in mice by avirulent Semliki Forest virus, Part 2 (An ultrastructural study of focal demyelination in the brain).
        Neuropath. Appl. Neurobiol. 1982; 2: 43-53
        • Kunkl A.
        • Klaus G.G.B.
        Selective effects of cyclosporin A on functional B cell subsets in the mouse.
        J. Immunol. 1980; 125: 2526
        • Mackenzie A.
        • Suckling A.J.
        • Jagelman S.
        • Wilson A.M.
        Histopathological and enzyme histochemical changes in experimental Semliki Forest virus infection in mice and their relevance to scrapie.
        J. Comp. Path. 1978; 88: 335
        • Niederberger N.
        • Lemaire M.
        • Maurer G.
        • Nussbaumer K.
        • Wagner O.
        Distribution and binding of cyclosporine in blood and tissues.
        in: Transplant. Proc.15. 1983: 2419-2421 (Suppl., 1/2)
        • Palestine A.G.
        • Nussenblatt R.B.
        • Chan C.
        Cyclosporine penetration into the anterior chamber and cerebrospinal fluid.
        Amer. J. Ophthalmol. 1985; 99: 210-211
        • Parker D.
        • Drossler K.
        • Turk J.L.
        Effect of cyclosporin A on antibody and cell mediated immune response.
        Int. J. Immunopharmac. 1984; 6: 67-74
        • Parsons L.M.
        • Webb H.E.
        Blood-brain barrier disturbance and immunoglobulin G levels in the cerebrospinal fluid of the mouse following peripheral infection with demyelinating Semliki Forest virus.
        J. Neurol. Sci. 1982; 57: 307-318
        • Parsons L.M.
        • Webb H.E.
        Virus titres and persistently raised white cell counts in the cerebrospinal fluid in mice after peripheral infection with demyelinating Semliki Forest virus.
        Neuropath. Appl. Neurobiol. 1982; 8: 395-401
        • Parsons L.M.
        • Webb H.E.
        Specific immunoglobulin G in serum and cerebrospinal fluid of mice infected with the demyelinating strain of Semliki Forest virus.
        Microbios Lett. 1984; 25: 135-140
        • Pathak S.
        • Illavia S.J.
        • Webb H.E.
        The identification and role of cells involved in CNS demyelination in mice after SFV infection: An ultrastructural study.
        in: Behan P.O. Ter Meulen V. Rose F.C. Immunology of Nervous System Infections. Progress in Brain Research. Vol. 59. Elsevier, Amsterdam1983: 237-254
        • Pessoa V.F.
        • Ikeda H.
        Increase in axonal transport in demyelinating optic nerve fibers in mice infected with Semliki Forest virus.
        Brain. 1984; 107: 433-446
        • Suckling A.J.
        • Pathak S.
        • Jagelman S.
        • Webb H.E.
        Virus associated demyelination a model using avirulent Semliki Forest virus infection of mice.
        J. Neurol. Sci. 1978; 36: 147-154
        • Suckling A.J.
        • Jagelman S.
        • Webb H.E.
        Immunoglobulin synthesis in nude (nu/nu), Math Eq and reconstituted nu/nu mice infected with an avirulent strain of Semliki Forest virus.
        Clin. Exp. Immunol. 1982; 47: 283-288
        • Sweny P.
        • Tidman N.
        The effect of cyclosporin A on peripheral blood T cell subpopulations in renal allografts.
        Clin. Exp. Immunol. 1982; 47: 445-448
        • Thomson A.W.
        • Moon D.K.
        • Inque Y.
        • Ceczy C.
        • Nelson D.S.
        Modification of delayed-type hypersensitivity reaction to ovalbumin in cyclosporin A treated guinea pigs.
        Immunology. 1983; 48: 301-308
        • Tremain K.E.
        • Ikeda H.
        Physiological deficits in the visual system of mice infected with Semliki Forest virus and their correlation with those seen in patients with demyelinating disease.
        Brain. 1983; 106: 879-895
        • Webb H.E.
        • Jagelman S.
        Viral infection of the CNS in the immune compromised host with special reference to certain paraneoplastic syndromes.
        in: Whitehouse J.M.A. Kay H.E. CNS Complications of Malignant Disease. Macmillan Press, London1979: 258-284