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. 1990 Aug;81(2):183–188. doi: 10.1111/j.1365-2249.1990.tb03315.x

Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats.

J A Voorthuis 1, B M Uitdehaag 1, C J De Groot 1, P H Goede 1, P H van der Meide 1, C D Dijkstra 1
PMCID: PMC1535058  PMID: 2117508

Abstract

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS) which causes paralysis. Several studies have reported the involvement of Ia antigen-expressing cells in the pathogenesis of EAE. Interferon-gamma (IFN-gamma) can induce Ia antigen expression on a wide range of cells. We examined the effect of IFN-gamma on EAE in Lewis rats. Systemically administered IFN-gamma did not change the disease course of EAE, whereas IFN-gamma applied locally into the ventricular system of the CNS resulted in complete suppression of clinical signs. Furthermore, we found that systemic administration of anti-IFN-gamma just prior to the onset of clinical symptoms resulted in a more severe disease course. We conclude that IFN-gamma is capable of exerting a suppressive action in EAE, possibly through induction of Ia antigen expression or through the induction of suppressive mechanisms locally in the CNS.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Billiau A., Heremans H., Vandekerckhove F., Dijkmans R., Sobis H., Meulepas E., Carton H. Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J Immunol. 1988 Mar 1;140(5):1506–1510. [PubMed] [Google Scholar]
  2. Brostoff S. W., Mason D. W. The role of lymphocyte subpopulations in the transfer of rat EAE. J Neuroimmunol. 1986 Feb;10(4):331–340. doi: 10.1016/S0165-5728(86)90016-0. [DOI] [PubMed] [Google Scholar]
  3. Cantell K., Schellekens H., Pyhälä L., Hirvonen S., Van der Meide P. H., De Reus A. Pharmacokinetic studies with human and rat interferons-gamma in different species. J Interferon Res. 1986 Dec;6(6):671–675. doi: 10.1089/jir.1986.6.671. [DOI] [PubMed] [Google Scholar]
  4. Dallman M. J., Wood K. J., Morris P. J. Cytotoxicity and IL 2 reactivity of cells from rejected or nonrejected allografts. Transplant Proc. 1988 Apr;20(2):226–228. [PubMed] [Google Scholar]
  5. Dijkema R., van der Meide P. H., Pouwels P. H., Caspers M., Dubbeld M., Schellekens H. Cloning and expression of the chromosomal immune interferon gene of the rat. EMBO J. 1985 Mar;4(3):761–767. doi: 10.1002/j.1460-2075.1985.tb03694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dijkstra C. D., Döpp E. A., Joling P., Kraal G. The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology. 1985 Mar;54(3):589–599. [PMC free article] [PubMed] [Google Scholar]
  7. Fontana A., Erb P., Pircher H., Zinkernagel R., Weber E., Fierz W. Astrocytes as antigen-presenting cells. Part II: Unlike H-2K-dependent cytotoxic T cells, H-2Ia-restricted T cells are only stimulated in the presence of interferon-gamma. J Neuroimmunol. 1986 Jul;12(1):15–28. doi: 10.1016/0165-5728(86)90093-7. [DOI] [PubMed] [Google Scholar]
  8. Fontana A., Fierz W., Wekerle H. Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature. 1984 Jan 19;307(5948):273–276. doi: 10.1038/307273a0. [DOI] [PubMed] [Google Scholar]
  9. Heremans H., Dijkmans R., Sobis H., Vandekerckhove F., Billiau A. Regulation by interferons of the local inflammatory response to bacterial lipopolysaccharide. J Immunol. 1987 Jun 15;138(12):4175–4179. [PubMed] [Google Scholar]
  10. Holt P. G., Degebrodt A., O'Leary C., Krska K., Plozza T. T cell activation by antigen-presenting cells from lung tissue digests: suppression by endogenous macrophages. Clin Exp Immunol. 1985 Dec;62(3):586–593. [PMC free article] [PubMed] [Google Scholar]
  11. Jonker M., Den Brok J. H. Idiotype switching of CD4-specific monoclonal antibodies can prolong the therapeutic effectiveness in spite of host anti-mouse IgG antibodies. Eur J Immunol. 1987 Nov;17(11):1547–1553. doi: 10.1002/eji.1830171104. [DOI] [PubMed] [Google Scholar]
  12. Massa P. T., ter Meulen V., Fontana A. Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4219–4223. doi: 10.1073/pnas.84.12.4219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matthaei I., Polman C. H., de Groot C. J., Dijkstra C. D., Koetsier J. C., Sminia T. Observer agreement in the assessment of clinical signs in experimental allergic encephalomyelitis. J Neuroimmunol. 1989 Jun;23(1):25–28. doi: 10.1016/0165-5728(89)90068-4. [DOI] [PubMed] [Google Scholar]
  14. McKernan L. N., Blank K. J., Spitalny G. L., Murasko D. M. Inhibition of macrophage-induced antigen-specific T-cell proliferation by interferon-gamma. Cell Immunol. 1988 Jul;114(2):432–439. doi: 10.1016/0008-8749(88)90334-6. [DOI] [PubMed] [Google Scholar]
  15. Mueller D. L. Do tolerant T cells exist? Nature. 1989 Jun 15;339(6225):513–514. doi: 10.1038/339513a0. [DOI] [PubMed] [Google Scholar]
  16. Noma T., Dorf M. E. Modulation of suppressor T cell induction with gamma-interferon. J Immunol. 1985 Dec;135(6):3655–3660. [PubMed] [Google Scholar]
  17. Panitch H. S., Hirsch R. L., Schindler J., Johnson K. P. Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system. Neurology. 1987 Jul;37(7):1097–1102. doi: 10.1212/wnl.37.7.1097. [DOI] [PubMed] [Google Scholar]
  18. Polman C. H., Dijkstra C. D., Sminia T., Koetsier J. C. Immunohistological analysis of macrophages in the central nervous system of Lewis rats with acute experimental allergic encephalomyelitis. J Neuroimmunol. 1986 May;11(3):215–222. doi: 10.1016/0165-5728(86)90005-6. [DOI] [PubMed] [Google Scholar]
  19. Reiber H., Suckling A. J., Rumsby M. G. The effect of Freund's adjuvants on blood-cerebrospinal fluid barrier permeability. J Neurol Sci. 1984 Jan;63(1):55–61. doi: 10.1016/0022-510x(84)90108-4. [DOI] [PubMed] [Google Scholar]
  20. Schober I., Braun R., Reiser H., Munk K., Leroux M., Kirchner H. la-positive T lymphocytes are the producer cells of interferon gamma. Exp Cell Res. 1984 Jun;152(2):348–356. doi: 10.1016/0014-4827(84)90636-0. [DOI] [PubMed] [Google Scholar]
  21. Skoglund C., Scheynius A., Holmdahl R., Van der Meide P. H. Enhancement of DTH reaction and inhibition of the expression of class II transplantation antigens by in vivo treatment with antibodies against gamma-interferon. Clin Exp Immunol. 1988 Mar;71(3):428–432. [PMC free article] [PubMed] [Google Scholar]
  22. Sminia T., de Groot C. J., Dijkstra C. D., Koetsier J. C., Polman C. H. Macrophages in the central nervous system of the rat. Immunobiology. 1987 Jan;174(1):43–50. doi: 10.1016/S0171-2985(87)80083-9. [DOI] [PubMed] [Google Scholar]
  23. Sriram S., Steinman L. Anti I-A antibody suppresses active encephalomyelitis: treatment model for diseases linked to IR genes. J Exp Med. 1983 Oct 1;158(4):1362–1367. doi: 10.1084/jem.158.4.1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Steiniger B., Falk P., Van der Meide P. H. Interferon-gamma in vivo. Induction and loss of class II MHC antigens and immature myelomonocytic cells in rat organs. Eur J Immunol. 1988 May;18(5):661–669. doi: 10.1002/eji.1830180502. [DOI] [PubMed] [Google Scholar]
  25. Steinman L., Rosenbaum J. T., Sriram S., McDevitt H. O. In vivo effects of antibodies to immune response gene products: prevention of experimental allergic encephalitis. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7111–7114. doi: 10.1073/pnas.78.11.7111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Svedersky L. P., Benton C. V., Berger W. H., Rinderknecht E., Harkins R. N., Palladino M. A. Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor. J Exp Med. 1984 Mar 1;159(3):812–827. doi: 10.1084/jem.159.3.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Thepen T., Van Rooijen N., Kraal G. Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med. 1989 Aug 1;170(2):499–509. doi: 10.1084/jem.170.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Unanue E. R., Beller D. I., Lu C. Y., Allen P. M. Antigen presentation: comments on its regulation and mechanism. J Immunol. 1984 Jan;132(1):1–5. [PubMed] [Google Scholar]
  29. Wong G. H., Bartlett P. F., Clark-Lewis I., Battye F., Schrader J. W. Inducible expression of H-2 and Ia antigens on brain cells. Nature. 1984 Aug 23;310(5979):688–691. doi: 10.1038/310688a0. [DOI] [PubMed] [Google Scholar]
  30. van der Meide P. H., Dubbeld M., Vijverberg K., Kos T., Schellekens H. The purification and characterization of rat gamma interferon by use of two monoclonal antibodies. J Gen Virol. 1986 Jun;67(Pt 6):1059–1071. doi: 10.1099/0022-1317-67-6-1059. [DOI] [PubMed] [Google Scholar]

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