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Pregnancy Can Set Stage for Autoimmune Diseases

Hormone fluctuation implicated in arthritis and MS

TUESDAY, Nov. 13, 2001 (HealthDayNews) -- A sharp drop in stress hormones after giving birth may cause flare-ups and even lead to arthritis and multiple sclerosis (MS) in some women, a new study says.

Rheumatoid arthritis and MS are autoimmune diseases, in which the body's immune system goes awry and mistakenly attacks tissues. In rheumatoid arthritis, the immune system attacks the joints, causing pain, swelling, stiffness and loss of function. In MS, the immune system attacks myelin, the fatty insulating material around nerve fibers in the brain and spinal cord. At its worst, MS causes partial paralysis.

During pregnancy, women's levels of certain stress hormones are very high, according to the study in the October issue of the Journal of Clinical Endocrinology and Metabolism.

These stress hormones are known to hinder the production of cytokines, the chemical messengers of the immune system, the study says. This mechanism is believed to play a role in preventing the mother's immune system from rejecting the embryo.

But after the baby is born, the levels of stress hormones plummet -- while the levels of immune system cytokines sharply rise.

"The finding has important implications for understanding why immune disorders may subside during pregnancy, but flare up again after birth," Dr. Duane Alexander, director of the National Institute of Child Health and Human Development (NICHD), says in a statement. "Understanding the immune processes involved may provide important new therapies for each of these conditions."

Researchers from the NICHD and the National Institute of Arthritis and Musculoskeletal and Skin Diseases charted the hormone levels in 18 women with normal, healthy pregnancies. The researchers measured the women's levels of stress hormones and immune hormones during the third trimester and shortly after giving birth.

The immune system cytokines were interleukin 12 and tumor necrosis factor alpha, which trigger the body's immune cells to ward off disease-causing invaders. The stress hormones were cortisol, 1,25 hydroxyvitamin D3 and norepinephrine, formerly called adrenaline, which help the body deal with stress.

During the third trimester of pregnancy, the levels of interleukin 12 and tumor necrosis factor were low. Meanwhile, the levels of the three stress hormones were high.

But after giving birth, the women's levels of immune system cytokines shot up to as much as three times higher than while they were pregnant, while stress hormone levels were two to three times lower.

The increase in stress hormones during pregnancy and the resulting suppression of the immune system is probably under the control of corticotropin releasing hormone, also known as "the master stress hormone," according to the study. Corticotropin releasing hormone is produced by the pituitary gland and the placenta in pregnant women.

"After birth, the supply of corticotropin releasing hormone plummets and the levels of the two immune hormones rise sharply," writes Dr. George P. Chrousos, the study's senior author and chief of the NICHD's Pediatric and Reproductive Endocrinology Branch. "This appears to result in a 'rebound' effect that could exacerbate disorders like rheumatoid arthritis and multiple sclerosis."

In an earlier study, Chrousos and his colleagues found the abrupt drop in corticotropin releasing hormone can result in postpartum depression in some women.

Rheumatoid arthritis and multiple sclerosis primarily strike women of childbearing age. MS, the most common neurological disorder among young adults, affects between 250,000 and 300,000 Americans, according to the National Multiple Sclerosis Society. The disease affects twice as many women as men. Rheumatoid arthritis also affects many more women than men, according to the National Arthritis Foundation.

Experts in the diseases say it's been known for decades that the symptoms of both disorders tend to abate during the third trimester of pregnancy and get worse afterwards, says Dr. John Klippel, medical director for the Arthritis Foundation in Atlanta.

"I would regard this as an important study," Klippel says. "It's been known for many years women with rheumatoid arthritis can improve during the third trimester of pregnancy. It's been long suspected that hormones play a role in the flare-up or the onset of rheumatoid arthritis. This study is trying to understand at a molecular level how the hormones lead to improvement during pregnancy and, similarly, flares or onset of rheumatoid arthritis post-partum."

Of course, he added, there is no one single reason why people develop arthritis or multiple sclerosis. Genetic predisposition probably plays a part.

New therapies to reduce the levels of cytokines such as tumor necrosis factor alpha are being developed, Klippel says. Likewise, researchers in other laboratories are experimenting with hormones as a possible treatment for multiple sclerosis, says Stephen Reingold, director of research for the National Multiple Sclerosis Society in New York City.

What To Do: For more information on arthritis and pregnancy, check out the Arthritis Foundation. You can read more about MS by clicking on the National Multiple Sclerosis Society.

SOURCES: Interviews with John Klippel, M.D., medical director, Arthritis Foundation, Atlanta; Stephen Reingold, Ph.D., director of research, National Multiple Sclerosis Society, New York; NICHD news release; October 2001 Journal of Clinical Endocrinology and Metabolism
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