Navigation Links
Estrogen fuels autoimmune liver damage
Date:4/30/2013

A life-threatening condition that often requires transplantation and accounts for half of all acute liver failures, autoimmune hepatitis is often precipitated by certain anesthetics and antibiotics. Researchers say these drugs contain tiny molecules called haptens that ever so slightly change normal liver proteins, causing the body to mistake its own liver cells for foreign invaders and to attack them. The phenomenon disproportionately occurs in women, even when they take the same drugs at the same doses as men.

Results of the new study, described in the April issue of the journal PLoS One, reveal that estrogen and a signaling molecule called interleukin-6 collude to form a powerful duo that leads to immune cell misconduct and fuels autoimmune liver damage.

The findings, the research team says, also suggest therapeutic strategies to curb damage in people who develop drug-induced liver inflammation.

"Our study shows that estrogen is not alone in its mischief but working with an accomplice to set off a cascade of events that leads to immune cell dysregulation and culminates in liver damage," says Dolores Njoku, M.D., a pediatric anesthesiologist and critical care expert at Johns Hopkins Children's Center.

In the study, led by Njoku, researchers induced liver inflammation in mice by injecting them with drug-derived haptens. Female mice developed worse liver damage than male mice, and castrated male mice fared worse than their intact brethren, likely due to loss of testosterone and altered estrogen-to-testosterone ratio, the researchers say. Female mice with missing ovaries the chief estrogen-secreting organs suffered milder forms of hepatitis than mice with intact ovaries.

Female mice produced more liver-damaging antibodies and more inflammation-triggering chemicals, specifically the inflammatory molecule interleukin-6, known to fuel autoimmunity. Liver damage was notably milder in female mice whose interleukin-6 receptors were blocked or missing compared with normal female mice. On the other hand, male mice and female mice with missing ovaries had nearly undetectable levels of interleukin-6, while castrated male mice showed simultaneous upticks in both estrogen and interleukin-6.

The research team further zeroed in on a class of cells known as regulatory T cells, whose main function is keeping tabs on other immune cells to ensure they don't turn against the body's own tissues. When researchers compared the number of regulatory T cells present in the spleens of male and female mice, they noticed far fewer regulatory T cells in the spleens of female mice. The spleen, the researchers explain, is the primary residence of mature immune cells.

"Deficiency of regulatory T cells effectively takes the reins off other immune cells, leading to overactive immunity," Njoku says.

In a final, dot-connecting move, the researchers immersed spleen-derived immune cells in estrogen. What they observed proved beyond doubt that estrogen, interleukin and regulatory T cells form a powerful triangle. Estrogen induced the immune cells of female mice to express more interleukin-6, which in turn diminished the expression of inflammation-taming regulatory T cells.

When the researchers injected sick female mice with a booster dose of regulatory T cells, their liver inflammation subsided to levels seen in male mice.

This powerful response, the researchers say, suggests that therapy with regulatory T cells may reduce estrogen-related liver damage in patients with autoimmune hepatitis. Such treatment, however, remains years away from human application.

One reason, the researchers say, is that regulatory T cells maintain the fine equilibrium between overactive and underactive immunity. Because an overactive immune system can lead to autoimmune diseases and an underactive one can promote tumor growth, any therapy with regulatory T cells must be precisely calibrated to avoid tipping this precarious balance.

"We first must figure out where the golden mean lies," Njoku says.


'/>"/>

Contact: Ekaterina Peshva
epeshev1@jhmi.edu
410-502-9433
Johns Hopkins Medicine
Source:Eurekalert

Related medicine news :

1. Estrogen Level in Pregnancy May Affect Breast Cancer Risk in Daughters
2. Estrogen plus progestin use linked with increased breast cancer incidence and mortality
3. Estrogen helps keep joint pain at bay after hysterectomy
4. Maturitas publishes clinical guide on low-dose vaginal estrogens for vaginal atrophy
5. Genetic markers for testosterone and estrogen level regulation identified
6. BUSM researchers identify genetic markers for testosterone, estrogen level regulation
7. Muscular Development Store Affirms Whey Protein Fuels Strong Workouts
8. 1 week and counting: Dont cut the research that fuels the US economy
9. Evidence on abortion figures overestimated in Mexico fuels scientific debate in medical journal
10. Autoimmune disease linked to pregnancy loss, stroke more often than you’d expect
11. Statins have potential to treat an autoimmune clotting disorder called antiphospholipid syndrome
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Apple Rehab Shelton ... staged a mock evacuation of the facility as part of a disaster drill on ... Echo Hose EMS and Shelton City Emergency Manager, as well as the Connecticut ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at The ... the most popular and least understood books in the Holy Scriptures, Revelation. The Book ... have baffled scholars for centuries. Many have tossed it off as mere rubbish, but ...
(Date:10/12/2017)... ... October 12, 2017 , ... First Healthcare ... program management, will showcase a range of technology and learning solutions at the ... Convention and Expo to be held October 14–18, 2017 at the Mandalay Bay ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... The American ... Excellence to Carol Friedman, PhD, FACMI, during the Opening Session of AMIA’s Annual Symposium ... 8. , In honor of Morris F. Collen, a pioneer in the field of ...
(Date:10/12/2017)... ... October 12, 2017 , ... Leading pediatric oncology experts at ... D.C., for the 49th Congress of the International Society of Paediatric Oncology ... the Center for Cancer and Blood Disorders at Children’s National, and Stephen ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... Sept. 28, 2017 Hill-Rom Holdings, Inc. (NYSE: ... conference call and webcast on Friday, November 3, 2017, ... and ending at approximately 8:30 a.m. (CDT) / 9:30 ... company,s 2017 financial performance and guidance for 2018, Hill-Rom ... to enhance operational performance, and long-range financial outlook through ...
(Date:9/25/2017)...   Montrium , an industry leader in ... IQPC Trial Master Files & Inspection Readiness Conference ... Clinical Services has selected eTMF Connect ... EastHORN, a leading European contract research organization (CRO), ... to enable greater collaboration with sponsors, improve compliance ...
(Date:9/22/2017)... 22, 2017 AVACEN Medical (AVACEN) announced that ... successfully helping those with the widespread pain associated with ... Amanda in Essex, England commented, ... hair, experiencing no sleep at all, tremendous pain, with ... cannot recommend [the AVACEN 100] enough, how this has ...
Breaking Medicine Technology: