Interleukin-6 Involved in the Development of Endometriosis

Targeting this molecule in the future may help prevent or treat endometriosis in the future.

Key Points

Highlights:

• IL-6 signaling may be involved in the development of endometriosis. 

Importance:

• Targeting this signaling pathway may constitute a potential therapeutic or preventative approach for endometriosis in the future.

What’s done here?

• Researchers analyzed the levels of macrophages, IL-6, and IL-6 receptor both in its soluble and membrane-binding form in the peritoneal fluid of women with endometriosis and those without.

Key results:

• Activated macrophages, IL-6, and membrane-binding IL-6 receptor were increased in the peritoneal fluid of all patients with endometriosis. 
• Levels of the soluble IL-6 receptor were increased in the peritoneal fluid of patients with moderate to severe endometriosis. 
• Levels of the membrane-binding IL-6 receptor were reduced in the blood of patients with moderate to severe endometriosis.

Limitations of the study:

• The study only involved 47 women with endometriosis.
• The study should be repeated at another center to confirm the findings 

Lay Summary

A chemical produced by the body called Interleukin-6 (IL-6) and known to be involved in inflammation also seems to promote the development of endometriosis. This is according to a study by Chinese scientists published in the journal Medical Science Monitor.

Previous research has shown that the concentration of IL-6 is increased in the peritoneal fluid (the liquid lubricating the surface of tissues lining the abdominal wall and pelvic cavity) of women with endometriosis. But it was not clear whether increased IL-6 was directly contributing to the development of endometriosis, or it was just a consequence of the disease. 

The current study evaluates the potential role of IL-6 and its receptor IL-6R (the protein to which IL-6 binds to exert its activity) in the development of endometriosis. The team of researchers led by Dr. RuiJin Wu at Zhejiang University in China analyzed 47 women with endometriosis and 22 women without endometriosis. Women with endometriosis were divided into two groups, those in the first group having stage 1 and two endometriosis — minimal to mild (19 women) and those in the second group, stage 3 and four endometriosis — moderate to severe (28 women). 

The team tested the peritoneal fluid to measure the levels of activated macrophages, the predominant immune system cells that secrete IL-6, and the expression of IL-6 and IL-6R. The latter was examined in its two forms: membrane-binding and soluble. 

They found that all women with endometriosis had more activated macrophages, more IL-6 and more membrane-binding IL-6R than the control group. However, the soluble form of the receptor was increased only in patients with moderate to severe endometriosis. Interestingly, those women also showed lower levels of membrane-binging IL-6R in their blood, suggesting that the soluble form of IL-6R found in the peritoneal fluid derives from the membrane-binding form discovered in the blood. 

It was already known that IL-6 stimulates the macrophages to release more IL-6 as well as another molecule called haptoglobin by activating IL-6R found on their surface. Haptoglobin inhibits the immune-surveillance function of macrophages by blocking their ability to engulf and kill other cells, including endometrial cells in the peritoneal cavity. Furthermore, the soluble form of the IL-6R, increases the availability of IL-6, finally resulting in a greater reduction in the immune-surveillance activity of the macrophages.  haptoglobin

By considering their results in this context, the researchers concluded that the increase of IL-6 and the soluble form of its receptor IL-6R in the peritoneal fluid promotes the development of endometriosis, 

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28779573