A critical role for IL-4 in regulating disease severity in experimental allergic encephalomyelitis as demonstrated in IL-4 deficient C57BL/6 mice and BALB/c mice

Marika Falcone, Alice J. Rajan, Barry R. Bloom, Celia F. Brosnan

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Abstract

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the central nervous system (CNS) that has served as the principal experimental model for multiple sclerosis (MS). Susceptibility to disease is thought to correlate with the ability to generate a Th1-type profile in myelin-responsive T cells, whereas T cells producing a Th2 cytokine pattern, in particular IL-4, are thought to be nonencephalitogenic and also to confer protection against a Th1-type response. However, recent studies using a variety of genetically engineered animals in which the genes for Th1-type cytokines and/or their receptors have been inactivated have called into question the Th1-Th2 paradigm in experimental allergic encephalomyelitis. In this report we have addressed the contribution of IL-4 to disease expression by studying two strains of mice, C57BL/6 and BALB/c, in which the gene for IL-4 has been inactivated. The IL-4-deficient C57BL/6 mice, and to a lesser extent the IL-4-deficient BALB/c mice, developed a more severe form of clinical disease, a more extensive pathologic involvement of the spinal cord, and an increased expression of proinflammatory cytokines in the CNS than their wild-type littermates. BALB/c and C57BL/6 mice showed a slightly different cytokine profile in the CNS. Both groups of animals recovered from the acute clinical episode in a time frame that was essentially identical to that found in the wild-type controls. We conclude that IL-4 plays an important role in modulating the severity of the encephalitogenic process, but does not by itself contribute to spontaneous remission the disease.

Original languageEnglish
Pages (from-to)4822-4830
Number of pages9
JournalJournal of Immunology
Volume160
Issue number10
Publication statusPublished - May 15 1998

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Autoimmune Experimental Encephalomyelitis
Inbred C57BL Mouse
Interleukin-4
Cytokines
Central Nervous System
T-Lymphocytes
Autoimmune Diseases of the Nervous System
Spontaneous Remission
Genetically Modified Animals
Disease Susceptibility
Myelin Sheath
Genes
Multiple Sclerosis
Spinal Cord
Theoretical Models

ASJC Scopus subject areas

  • Immunology

Cite this

A critical role for IL-4 in regulating disease severity in experimental allergic encephalomyelitis as demonstrated in IL-4 deficient C57BL/6 mice and BALB/c mice. / Falcone, Marika; Rajan, Alice J.; Bloom, Barry R.; Brosnan, Celia F.

In: Journal of Immunology, Vol. 160, No. 10, 15.05.1998, p. 4822-4830.

Research output: Contribution to journalArticle

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abstract = "Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the central nervous system (CNS) that has served as the principal experimental model for multiple sclerosis (MS). Susceptibility to disease is thought to correlate with the ability to generate a Th1-type profile in myelin-responsive T cells, whereas T cells producing a Th2 cytokine pattern, in particular IL-4, are thought to be nonencephalitogenic and also to confer protection against a Th1-type response. However, recent studies using a variety of genetically engineered animals in which the genes for Th1-type cytokines and/or their receptors have been inactivated have called into question the Th1-Th2 paradigm in experimental allergic encephalomyelitis. In this report we have addressed the contribution of IL-4 to disease expression by studying two strains of mice, C57BL/6 and BALB/c, in which the gene for IL-4 has been inactivated. The IL-4-deficient C57BL/6 mice, and to a lesser extent the IL-4-deficient BALB/c mice, developed a more severe form of clinical disease, a more extensive pathologic involvement of the spinal cord, and an increased expression of proinflammatory cytokines in the CNS than their wild-type littermates. BALB/c and C57BL/6 mice showed a slightly different cytokine profile in the CNS. Both groups of animals recovered from the acute clinical episode in a time frame that was essentially identical to that found in the wild-type controls. We conclude that IL-4 plays an important role in modulating the severity of the encephalitogenic process, but does not by itself contribute to spontaneous remission the disease.",
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