Sharp Drop In Stress Hormones May Set Stage For Arthritis, Multiple Sclerosis After Pregnancy

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A sharp drop in stress hormones after giving birth to a child may predispose some women to develop certain conditions in which the immune system attacks the body’s own tissues, according to researchers at the National Institutes of Health.

The study was conducted by researchers at the National Institute of Child Health and Human Development (NICHD) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The study appeared in the October issue of The Journal of Clinical Endocrinology and Metabolism.

"This finding has important implications for understanding why immune disorders may subside during pregnancy, but flare up again after birth,” Duane Alexander, M.D., director of the NICHD. “Understanding the immune processes involved may provide important new therapies for each of these conditions.”

Rheumatoid arthritis (RA) is a disorder in which the immune system apparently causes pain, swelling, stiffness, and loss of function in the joints. In multiple sclerosis, the immune system attacks the brain and nervous system.

The immune hormones Interleukin 12 (IL-12) and tumor necrosis factor alpha TNF alpha hormones are involved in triggering the body’s immune cells to ward off disease causing invaders, explained the study’s senior investigator, George P. Chrousos, M.D., Chief of NICHD’s Pediatric and Reproductive Endocrinology Branch. Both hormones also seem to be involved in the swelling and tissue destruction seen in rhematoid arthritis and multiple sclerosis. Similarly people with these conditions also have higher-than-normal amounts of the two immune hormones.

In pregnant women who have either multiple sclerosis or rheumatoid arthritis, symptoms may ease up or even disappear during the third trimester of pregnancy, Dr. Chrousos said. After the women give birth, however, their symptoms often return. Similarly, pregnant women who do not have either disorder may develop one of them within a year of giving birth.

The researchers recruited 18 women with normal, healthy pregnancies for their study. Next, the researchers charted the women’s levels of IL-12 and TNF alpha in the third trimester of pregnancy as well as within the weeks following the birth of their child. The investigators found that, during the third trimester of pregnancy, the women’s levels of IL-12 was about three times lower than it was after they had given birth. Similarly, the women’s TNF alpha levels were 40 percent lower during the third trimester than it was after birth.

The researchers also found, however, that the women’s levels of the stress hormones cortisol, norepinephrine (formerly adrenalin) and 1,25 hydroxyvitamin D3 were two to three times higher than they were after the women had given birth. All three hormones are produced to help the body respond to a stress. The most well known of these, norepinephrine, is involved in the “fight or flight” response, in which strength and reflexes are enhanced, to escape or deal with a possible threat. Other research has shown that all three of these stress hormones serve to hinder the production of immune system hormones.

The increase in these stress hormones is probably caused by the master stress hormone, corticotropin releasing hormone (CRH). This hormone is produced in the pituitary gland in response to stress, and ultimately signals the production of cortisol, norepinephrine, and 1,25 hydroxyvitamin D3. Similarly, CRH is also produced by the placenta.

“It appears as if suppression of IL-12 and TNF alpha results indirectly from the the CRH the placenta produces,” Dr. Chrousos said. “After birth, the supply of CRH plummets and the levels of the two immune hormones rise sharply. This appears to result in a ‘rebound’ effect that could exacerbate disorders like rheumatoid arthritis and multiple sclerosis.”

In one earlier study, Dr. Chrousos and his coworkers found that an abrupt drop in CRH after birth resulted in post partum depression in some women. In a more recent study, they showed that production of CRH by the placenta and the uterine lining played a role in preventing the mother’s immune system from rejecting the early embryo. 

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