Summary
Experimental allergic neuritis (EAN) was induced in guinea pigs and rats and treated with Cyclosporin-A (Cy-A). When Cy-A was given prophylactically for 1 month from the time of induction of the disease, it prevented the development of EAN during the course of its administration. When Cy-A was given therapeutically after the onset of neurological signs, it effectively prevented further deterioration. This effect was more marked after 3 weeks' treatment than after only 1 week's treatment.
In both regimens, when dosing with Cy-A ceased there was a latent period before clinical signs of EAN developed. This latent period is similar to that seen in the development of EAN in normal control animals and is probably due to the continued presence of antigen at the injection sites. After primary treatment of EAN with Cy-A, animals that relapsed did not respond to further treatment with Cy-A.
Histological examination revealed that the nature of the EAN lesions in both groups of animals given Cy-A were not as severe as those seen in control animals. Despite these observations, there was no statistically significant difference between the maximum clinical grades reached by animals in any one group.
These experiments suggest that T-cells are important in the development of EAN and that Cy-A interferes with this process by suppressing T-helper cells. They also show that it is possible to influence favourably the course of immune mediated neurological disease.
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References
Adams CW, Abdulla YH, Turner DR, Bayliss OB (1968) Subcellular preparation of peripheral nerve myelin. Nature 220:171–173
Anthony JH, Pollard JD, McLeod JG (1981) Effects of plasmapheresis on the course of experimental allergic neuritis in rabbits. J Neurol Neurosurg Psychiat 44:1124–1128
Arnason BGW (1970) The inflammatory lesion in idiopathic polyneuritis compared to that in experimental allergic neuritis. In: Proceedings Sixth International Congress of Neuropathology. Masson, Paris, pp 691–699
Ballin RHM, Thomas PK (1969) Electron microscope observations on demyelination and remyelination in experimental allergic neuritis. Part 1. Demyelination. J Neurol Sci 8:1–18
Bolton C, Cuzner ML (1980) Modification of EAE by nonsteroidal anti-inflammatory drugs. In: Davison AD, Cuzner ML (eds) The suppression of experimental allergic encephalomyelitis and multiple sclerosis. Academic Press, London, pp 189–197
Borel JF, Feurer C, Gubler HU, Stähelin H (1976) Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Act 6:468–475
Borel JF, Feurer C, Magnée C, Stähelin H (1977) Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology 32:1017–1025
Bunjes D, Hardt C, Solbach W, Deusch K, Röllinghoff M, Wagner H (1982) Studies on the mechanism of action of Cyclosporin A in the murine and human T-cell response in vitro In: White DJG (ed) Cyclosporin A. Elsevier Biomed. Press, Amsterdam New York, pp 261–280
Burckhardt JJ, Guggenheim B (1979) Cyclosporin A: in vivo and in vitro suppression of rat T-lymphocyte function. Immunology 36:753–757
Cammisuli S (1982) The effect of Cyclosporin A on cell interactions within the immune system. In: White DJG (ed) Cyclosporin A. Elsevier Biomed. Press, Amsterdam New York, pp 243–259
Carlo DJ, Karkhanis YD, Bailey PJ, Wiśniewski HM, Brostoff SW (1975) Experimental allergic neuritis: evidence for the involvement of the P0 and P2 proteins. Brain Res 88:580–584
Caspary EA, Field EJ (1965) Antibody response to central and peripheral nerve antigens in rat and guinea pig. J Neurol Neurosurg Psychiat 28:179–182
Dal Canto MC, Johnson AB, Raine CS, Wiśniewski HM, Brostoff SW (1974) Experimental allergic neuritis: Cells binding horseradish conjugates of myelin basic proteins. J Immunol 113:387–394
Gross MLP, Craggs RI (1982) The treatment of experimental allergic neutitis by plasma exchange. Vth Int. Congr. Neuromuscular Diseases, Marseille, France, Sept. 12–18th, p 28–1.
Hess AD, Tutschka PJ, Santos GW (1982) The effect of Cyclosporin A on T-lymphocyte subpopulations. In: White DJG (ed) Cyclosporin A, Elsevier Biomed. Press, Amsterdam New York, pp 209–231
Karnovsky MJ (1965) A formaldehyde—glutaraldehyde fixative of high osmolarity for use in electron microscopy. J Cell Biol 27:137A
Klaus GGB (1981) The effects of cyclosporin A on the immune system. Immunol Today 2:83–87
Kunkl A, Klaus GGB (1980) Selective effects of cyclosporin A in functional B cell subsets in the mouse. J Immunol 125:2526–2531
Lampert PW (1969) Mechanism of demyelination in experimental allergic neuritis. Lab Invest 20:127–138
Levine S, Sowinski R (1977) Suppression of the hyperacute form of experimental allergic encephalomyelitis by drugs. Arch Int Pharmacodyn 230:309–318
Norton WT, Poduslo SE (1973) Myelination in rat brain: Method of myelin isolation. J Neurochem 21:749–757
Pepys MD (1979) Experimental allergic neuritis. In: Rose FC (ed) Clinical neuroimmunology. Blackwell, Oxford, pp 155–164
Saida T, Saida K, Silberberg DH, Brown MJ (1978) Transfer of demyelination by intraneural injection of experimental allergic neuritis serum. Nature 272:639–641
Saida K, Saida T Brown MJ, Silberberg DH, Asbury AK (1978) Antiserum-mediated demyelination in vivo. A sequential study using intraneural injection of experimental allergic neuritis serum. Lab Invest 39:449–462
Sievers J (1971) Basic two-dye stains for epoxy-embedded 0.3–1μ sections. Stain Technol 46:195–199
Tompkins C, King RHM, Thomas PK (1980) Modification of experimental allergic neuritis by Cyclosporin A. Neuropathol Appl Neurobiol 6:240
Waksman BH, Adams RD (1955) Allergic neuritis: an experimental disease of rabbits induced by the injection of peripheral nervous tissue and adjuvants. J Exp Med 102:213–234
Waksman BH, Adams RD (1956) A comparative study of experimental allergic neuritis in rabbit, guinea-pig and mouse. J Neuropathol Exp Neurol 15:293–374
White DJG, Plumb AM, Pawelec G, Brons G (1979) Cyclosporin A: An immunosuppressive agent preferentially active against proliferating T cells. Transplantation 27:55–58
Yonezawa T, Ishihara Y, Matsuyama H (1968) Studies on experimental peripheral neuritis. 1. Demyelinating patterns studied in vitro. J Neuropathol Exp Neurol 27:453–463
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King, R.H.M., Craggs, R.I., Gross, M.L.P. et al. Suppression of experimental allergic neuritis by cyclosporin-A. Acta Neuropathol 59, 262–268 (1983). https://doi.org/10.1007/BF00691491
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DOI: https://doi.org/10.1007/BF00691491