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Transgenic interleukin 10 prevents induction of experimental autoimmune encephalomyelitis.

Abstract
The effectiveness of interleukin 10 (IL-10) in the treatment of autoimmune-mediated central nervous system inflammation is controversial. Studies of the model system, experimental autoimmune encephalomyelitis (EAE), using various routes, regimens, and delivery methods of IL-10 suggest that these variables may affect its immunoregulatory function. To study the influence of these factors on IL-10 regulation of EAE pathogenesis, we have analyzed transgenic mice expressing human IL-10 (hIL-10) transgene under the control of a class II major histocompatibility complex (MHC) promoter. The hIL-10 transgenic mice are highly resistant to EAE induced by active immunization, and this resistance appears to be mediated by suppression of autoreactive T cell function. Myelin-reactive T helper 1 cells are induced but nonpathogenic in the IL-10 transgenic mice. Antibody depletion confirmed that EAE resistance is dependent on the presence of the transgenic IL-10. Mice expressing the hIL-10 transgene but not the endogenous murine IL-10 gene demonstrated that transgenic IL-10 from MHC class II-expressing cells is sufficient to block induction of EAE. This study demonstrates that IL-10 can prevent EAE completely if present at appropriate levels and times during disease induction.
AuthorsD J Cua, H Groux, D R Hinton, S A Stohlman, R L Coffman
JournalThe Journal of experimental medicine (J Exp Med) Vol. 189 Issue 6 Pg. 1005-10 (Mar 15 1999) ISSN: 0022-1007 [Print] United States
PMID10075984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Myelin Basic Protein
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
Topics
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental (prevention & control)
  • Female
  • Interferon-gamma (biosynthesis)
  • Interleukin-10 (physiology)
  • Interleukin-4 (biosynthesis)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Myelin Basic Protein (immunology)
  • Th1 Cells (physiology)

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