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Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis

Gene Therapy volume 8, pages 769–777 (2001)Cite this article

Abstract

We have used interleukin (IL)-4 and -10-producing HSV-1 γ134.5 deletion viruses in gene therapy of a BALB/c model of experimental allergic encephalomyelitis (EAE), a T cell-mediated demyelinating disease of the central nervous system. It is known that in EAE of mice the Th2-type cytokines are down-regulated and the Th1-type cytokines up-regulated during the onset and relapse of the disease. Therefore, we tested two HSV-1 recombinants expressing the Th2-type cytokines IL-4 and IL-10. The recombinant viruses were injected intracranially (i.c.) in BALB/c mice 6 days after induction of EAE. As control groups we used mice without any infection, mice infected with backbone virus R3659 and mock-infected mice. Weights and symptoms of the mice were recorded daily and the tissue specimens were collected at specific time-points. The results indicate that the intracranial infection with IL-4-producing virus (1) precludes EAE symptoms, (2) protects the spinal cord from massive leukocyte infiltrations and (3) prevents demyelination and axonal loss. The IL-10-expressing virus R8308 did not have a similar favorable effect on the recovery of the mice as did the IL-4 virus R8306. Gene Therapy (2001) 8, 769–777.

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Acknowledgements

This study was financially supported by Turku Graduate School of Biomedical Sciences, the Finnish Cultural Foundation, the Turku University Foundation and the Turku University Central Hospital. We are also grateful for the technical assistance of Mika Venojärvi and skillful animal care of Seija Lindqvist.

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Authors and Affiliations

  1. Department of Virology, University of Turku, Turku, Finland

    E Broberg, N Setälä, A Salmi, J-P Erälinna & V Hukkanen

  2. MediCity Research Laboratory, University of Turku, Turku, Finland

    E Broberg & V Hukkanen

  3. Turku Graduate School of Biomedical Sciences, Turku, Finland

    E Broberg & N Setälä

  4. Department of Pathology, University of Turku, Turku, Finland

    M Röyttä

  5. Department of Neurology,, University of Turku, Turku, Finland

    J-P Erälinna

  6. The Marjorie B Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL, USA

    B He & B Roizman

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Broberg, E., Setälä, N., Röyttä, M. et al. Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis. Gene Ther 8, 769–777 (2001). https://doi.org/10.1038/sj.gt.3301465

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  • DOI: https://doi.org/10.1038/sj.gt.3301465

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