Lower relapse rates in multiple sclerosis patients during pregnancy result from higher levels of estrogen leading to NF-kB inhibition.
Women with multiple sclerosis have been reported to suffer fewer relapses (attacks or disease exacerbations) during the time of pregnancy. While there has been some controversy on this issue, the PRIMS study (pregnancy and MS study) documented a modest but significant decrease in the rate of relapse in 227 women with MS during pregnancy, especially during the third trimester. Those same women then experienced a higher than normal (pre-pregnancy) rate of relapse following childbirth, especially in the first three months after childbirth.
Increased estrogen (or estriol) levels during pregnancy have been postulated as the source of this ‘protective effect’.
In the study summarized below, the researchers note the effects of estriol on various mediators of inflammation and on the inhibition of NF-kB.
Specifically associated with higher levels of estriol:
- Inhibition of T-cell transmigration (into the CNS.)
- Decreased T cell expression of matrix metalloproteinase-9 (a destructive enzyme)
- Increased production of IL-10 (an anti-inflammatory cytokine.)
- Decreased production of TNF-alpha (pro-inflammatory.)
The authors conclude that estriol regulates T-cell function (in a way that is beneficial to those with MS) by inhibiting NF-kB.
It seems reasonable to conclude that inhibition of NF-kB by other means might confer the same (or greater) protection against relapse in MS.
The publication:
J Neuroimmunol. 2002 Mar;124(1-2):106-14.
Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-kappa B.
Zang YC, Halder JB, Hong J, Rivera VM, Zhang JZ.
Multiple Sclerosis Research Unit, Baylor-Methodist Multiple Sclerosis Center and Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Summary of the abstract
The protective role of pregnancy in autoimmune conditions, such as multiple sclerosis (MS), is potentially associated with immune regulation by sex hormones produced during pregnancy.
This study was undertaken to examine the regulatory effects of estriol on the T cell functions, including transmigration and the cytokine production. The results revealed for the first time that estriol significantly inhibited T cell transmigration at a concentration range typical of pregnancy, which correlated with decreased T cell expression of matrix metalloproteinase-9.
Estriol was also found to alter the cytokine profile of T cells toward Th2 phenotype by up-regulating the production of IL-10 and inhibiting TNFalpha secretion of T cells.
Estriol inhibited nuclear transcription factor kappa B (NF-kB), which controls a variety of immune-related genes. This study provides new evidence that estriol is a potent regulator for the T cell functions potentially through its interaction with the NF-kappa B signaling pathway.
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