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-kappaB activation.
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 multiple sclerosis) by inhibiting NF-kappaB.
It seems reasonable to conclude that inhibition of NF-kappaB by other means might confer similar (perhaps greater) protection against relapse in MS.
Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-kappa B.
Summary of the abstract
The protection which appears conferred by pregnancy in autoimmune conditions such as multiple sclerosis, may result from immune modulation by hormones produced in greater amounts during gestation.
This study examined the effect of estrogen on T cell functions, including migration and cytokine production. The results revealed for the first time that estriol significantly inhibited T cell migration.
Estriol was found to alter the cytokines produced by T cells. More IL-10 (anti-inflammatory) was produced and less TNF (pro-inflammatory) was produced.
Estriol appeared to act by inhibiting NF-kappaB, which controls a variety of immune functions. This suggests that estriol is a potent regulator for the T cell functions by means of its effects on NF-kappaB.