Estrogen treatment down-regulates TNF-α production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice

A. Ito, Jr Bebo B.F., A. Matejuk, A. Zamora, M. Silverman, A. Fyfe-Johnson, Halina Offner

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Abstract

A shift toward Th2 cytokine production has been demonstrated during pregnancy and high dose estrogen therapy and is thought to be the primary mechanism by which estrogen suppresses the development of experimental autoimmune encephalomyelitis. However, low dose estrogen treatment is equally protective in the absence of a significant shift in cytokine production. In this study cytokine-deficient mice were treated with estrogen to determine whether a shift in Th2 cytokine production was required for the protective effects of hormone therapy. Estrogen effectively suppressed the development of experimental autoimmune encephalomyelitis in IL-4 and IL-10 knockout mice and in wild type littermate mice with a similar potency of protection. Significant disease suppression was also seen in IFN-γ-deficient mice. The decrease in disease severity was accompanied by a concomitant reduction in the number of proinflammatory cytokine- and chemokine-producing cells in the CNS. Although there was no apparent increase in compensatory Th2 cytokine production in cytokine-deficient mice, there was a profound decrease in the frequency of TNF-αproducing cells in the CNS and the periphery. Therefore, we propose that one mechanism by which estrogen protects females from the development of cell-mediated autoimmunity is through a hormone-dependent regulation of TNF-α production.

Original languageEnglish (US)
Pages (from-to)542-552
Number of pages11
JournalJournal of Immunology
Volume167
Issue number1
StatePublished - Jul 1 2001
Externally publishedYes

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Autoimmune Experimental Encephalomyelitis
Knockout Mice
Estrogens
Down-Regulation
Cytokines
Hormones
Autoimmunity
Chemokines
Interleukin-4
Interleukin-10
Pregnancy
Therapeutics

ASJC Scopus subject areas

  • Immunology

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Estrogen treatment down-regulates TNF-α production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. / Ito, A.; Bebo B.F., Jr; Matejuk, A.; Zamora, A.; Silverman, M.; Fyfe-Johnson, A.; Offner, Halina.

In: Journal of Immunology, Vol. 167, No. 1, 01.07.2001, p. 542-552.

Research output: Contribution to journalArticle

Ito, A. ; Bebo B.F., Jr ; Matejuk, A. ; Zamora, A. ; Silverman, M. ; Fyfe-Johnson, A. ; Offner, Halina. / Estrogen treatment down-regulates TNF-α production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. In: Journal of Immunology. 2001 ; Vol. 167, No. 1. pp. 542-552.
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