Inflammatory Agent in IBD, TNF-alpha, Found to Also Promote Healing in Colon

Inflammatory Agent in IBD, TNF-alpha, Found to Also Promote Healing in Colon

Researchers discovered that the molecule TNF-alpha has a dual role in inflammatory bowel disease (IBD). While long known to promote the disease, TNF-alpha has also been found to promote key immune regulatory cells, called M cells. The study on the discovery, “Induction of Colonic M Cells during Intestinal Inflammation,” was published in The American Journal of Pathology.

IBD is characterized by chronic inflammation of all or some of the digestive tract, caused by TNF-alpha, a proinflammatory cytokine produced by the body’s cells.

Researchers in the School of Medicine, University of California, Riverside, however, discovered that TNF-alpha has a dual role — while it promotes inflammation, it also induces immune surveillance cells in the colon called M cells.

“The induction of M cells by TNF-alpha suggests that the body may have a built-in system that promotes the inflammation as well as regulates and ultimately suppresses the response,” David Lo, a distinguished professor of biomedical sciences and study lead author, said in a press release. “If we don’t know what triggers the disease then the best we can do is treat the disease by suppressing inflammation. Currently, the main drug therapeutics being used to manage IBD are anti-inflammatory treatments. One of the newest is a series of biologicals — basically antibodies — that absorb the inflammatory molecules that promote the inflammatory response. There are half a dozen of these biologicals — specifically targeting the cytokine TNF-alpha. They don’t work in all patients, resulting often in some patients having to try one biological after another to find out what works.”

In other words, while TNF-alpha promotes inflammation and the destruction of tissues, it also promotes tissue healing.

“Cytokines are regulators of host responses to infection and inflammation,” Dr. Lo added. “Some make disease worse because they are proinflammatory. Others reduce inflammation and promote healing because they are anti-inflammatory. TNF-alpha plays a dual role in that it does both. If we had a more focused way of dealing with the undesired inflammatory aspects of TNF-alpha, we could still retain the healing, restorative aspects of this cytokine.”

Dr. Lo’s team discovered that in IBD, TNF-alpha induces an increase in the number of M cells. “They show up in the colon where they didn’t exist before, alerting the immune system that something is up. Through the M cells and their selective gatekeeping, the immune system is able to do some sampling of the gut — both more frequently and along the whole intestine. The colon is not normally a place where you have this sort of sampling going on. To significantly ramp up the sampling process by these M cells this way can help us figure out how the immune response will gear up its ability to either deliver a more powerful immune response or, alternatively, regulate and suppress the inflammation, and thus restore normal homeostasis in the intestine,” he said.

These findings may promote the development of novel, more efficacious therapies. They also help researchers to better understand the underlying mechanisms of IBD.

“Advanced immune surveillance is a clue into how the immune system is attempting to restore balance and calm in the tissues. If M cell production is a critical part of this restoration process, then it means we can develop more targeted therapies that don’t block this restoration,” Dr. Lo concluded. “Many of the biologicals being used today absorb and wipe out TNF-alpha, but in the long run this may be harmful to the patient because removing TNF-alpha altogether also blocks its ability to produce restorative mechanisms.”

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