Preliminary studies of cytokine secretion patterns associated with pregnancy in MS patients

Gilmore, Wendy; Arias, M.; Stroud, Nicole; Stek, Alice; McCarthy, Kathleen A.; Correale, Jorge

doi:10.1016/j.jns.2004.06.011

Cited by 56 publications

(32 citation statements)

References 55 publications

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“…During late pregnancy, there is a downregulation of Th1 and an increase in Th2 immune responses, which may underlie disease amelioration during this time (Whitacre et al, 1999;Kruse et al, 2000;Tchorzewski et al, 2000;Elenkov et al, 2001;Voskuhl, 2003;Al-Shammri et al, 2004;Gilmore et al, 2004). In a pilot clinical trial, nonpregnant female MS patients were treated with estriol to induce a pregnancy level in serum.…”

Section: Discussionmentioning

confidence: 99%

Treatment with an Estrogen Receptor Ligand Is Neuroprotective in Experimental Autoimmune Encephalomyelitis

Morales

Loo

Liu

et al. 2006

Journal of Neuroscience

140

132

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Multiple sclerosis is an inflammatory, neurodegenerative disease for which experimental autoimmune encephalomyelitis (EAE) is a model. Treatments with estrogens have been shown to decrease the severity of EAE through anti-inflammatory mechanisms. Here we investigated whether treatment with an estrogen receptor ␣ (ER␣) ligand could recapitulate the estrogen-mediated protection in clinical EAE. We then went on to examine both anti-inflammatory and neuroprotective mechanisms. EAE was induced in wild-type, ER␣-, or ER␤-deficient mice, and each was treated with the highly selective ER␣ agonist, propyl pyrazole triol, to determine the effect on clinical outcomes, as well as on inflammatory and neurodegenerative changes. ER␣ ligand treatment ameliorated clinical disease in both wild-type and ER␤ knock-out mice, but not in ER␣ knock-out mice, thereby demonstrating that the ER␣ ligand maintained ER␣ selectivity in vivo during disease. ER␣ ligand treatment also induced favorable changes in autoantigen-specific cytokine production in the peripheral immune system [decreased TNF␣, interferon-␥, and interleukin-6, with increased interleukin-5] and decreased CNS white matter inflammation and demyelination. Interestingly, decreased neuronal staining [NeuNϩ (neuronal-specific nuclear protein)/␤3-tubulinϩ/Nissl], accompanied by increased immunolabeling of microglial/monocyte (Mac 3ϩ) cells surrounding these abnormal neurons, was observed in gray matter of spinal cords of EAE mice at the earliest stage of clinical disease, 1-2 d after the onset of clinical signs. Treatment with either estradiol or the ER␣ ligand significantly reduced this gray matter pathology. In conclusion, treatment with an ER␣ ligand is highly selective in vivo, mediating both anti-inflammatory and neuroprotective effects in EAE.

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Section: Discussionmentioning

confidence: 99%

Treatment with an Estrogen Receptor Ligand Is Neuroprotective in Experimental Autoimmune Encephalomyelitis

Morales

Loo

Liu

et al. 2006

Journal of Neuroscience

140

132

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show abstract

“…[7][8][9][10] In addition, these studies did not identify which T-cell subset was producing the cytokines of interest. Thus, it is unclear if the immuno-logical changes they observed are best explained by pregnancy, MS, MS disease activity, or other factors, such as lactational amenorrhea.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Interferon-γ–Producing T Cells, Pregnancy, and Postpartum Relapses of Multiple Sclerosis

Langer‐Gould¹,

Gupta²,

Huang³

et al. 2010

Arch Neurol

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“…Thus, mechanisms other than sCD95 might be responsible for the suppressive effect of pregnancy on MS. Pregnancy has long been considered to be a Th2-related occurrence [18,19]. However, it has recently been reported that gravidity is instead associated with an increased production of regulatory IL-10 [20] and an expansion of CD4 + CD25 + and IL-10 + regulatory T cells [21]. This indicates that the hormone-mediated improvement of regulatory immune mechanisms could have a beneficial effect on MS disease course.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of soluble CD95 are not associated with amelioration of multiple sclerosis during pregnancy

Ehrlich

Haas²,

Zipp

et al. 2007

Journal of the Neurological Sciences

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Preliminary studies of cytokine secretion patterns associated with pregnancy in MS patients

Cited by 56 publications

References 55 publications

Treatment with an Estrogen Receptor Ligand Is Neuroprotective in Experimental Autoimmune Encephalomyelitis

Treatment with an Estrogen Receptor Ligand Is Neuroprotective in Experimental Autoimmune Encephalomyelitis

Interferon-γ–Producing T Cells, Pregnancy, and Postpartum Relapses of Multiple Sclerosis

Serum levels of soluble CD95 are not associated with amelioration of multiple sclerosis during pregnancy

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