The Role of Small Proteins in Inflammatory Bowel Disease

Cytokine IL-36 found to drive some inflammatory processes while helping to resolve the inflammation in IBD patients.

Researchers have found that small proteins play an important role in regulating inflammation during inflammatory bowel disease (IBD), which affects approximately 1.5 million Americans.

During a study published in The Journal of Immunology, researchers found that a cytokine called IL-36 was expressed in inflamed intestines of mice and looked to explore its role in the disease.

"What we found was quite striking," said lead study author Tim Denning. "If we block the effects of this cytokine, IL-36, in a mouse model of intestinal inflammation, the mice were better and had less disease early on, which suggested that this was a pro-inflammatory cytokine. However, when we assessed the ability of mice deficient in the receptor for IL-36 to heal, which is a vital part of resolving intestinal inflammation, they were completely unable to do so. The study highlights the important role of IL-36, not only in driving some of the inflammatory process, but also in helping to resolve the inflammation."

Normally, the immune system does not act aggressively towards the trillions of good bacteria found in the intestines because they are helpful to the human body. However, patients suffering from IBD have an immune system that fights against the bacteria.

Researchers at Georgia State University, Emory University, University of Michigan, and Amgen explored factors that could contribute to the regulation of immune system balance in tolerating bacteria or reacting aggressively against them.

The results of the study showed that IL-36 promoted intestinal inflammation and healed inflammation.

"Treatments that block certain factors, regardless of knowing the role it may be playing at a certain stage of disease, could lead to a poor outcome and may be the reason some clinical trials fail," Denning said. "It is key to understand what phase of disease patients are in, what cytokines are expressed and the appropriate therapeutic targets during these distinct phases. Oftentimes, blocking a factor is not universally beneficial. Immune responses and inflammation, which are often viewed as deleterious, can be both good and bad depending on the context."