Cytokine Once Thought Only to Promote Inflammation Now Seen to Have Restorative Properties, Too

Researchers at the School of Medicine of the University of California (UC), Riverside, found that TNF-alpha, a factor known for its pro-inflammatory actions, also triggers processes that end inflammation by inducing a type of immune surveillance cell, called M-cells. By advancing our understanding of immune processes, the finding may lead to more specific treatments for multiple sclerosis (MS) and other autoimmune diseases.

“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,” said David Lo, the study’s senior author and a professor of biomedical sciences at UC Riverside, said in a press release.

TNF-alpha has been observed to drive inflammation and induce tissue damage in several autoimmune diseases by triggering the production of other inflammatory molecules. But, as the finding showed, it can also stimulate tissue repair by resolving inflammation.

“Cytokines are regulators of host responses to infection and inflammation,” Dr. Lo said. “Some make disease worse because they are pro-inflammatory. 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.”

In the study, titled “Induction of Colonic M Cells during Intestinal Inflammation” and published in The American Journal of Pathology, the research team explored TNF-alpha in the gut of mice, focusing on inflammatory bowel disease (IBD) — an inflammatory condition often treated with anti-TNF-alpha antibodies, entirely removing the actions of the signaling factor.

Such an approach is not used in MS because these drugs increase disease activity, a finding that might be linked to the dual actions of TNF-alpha. While the study did not attempt to address this issue, its results might provide clues to MS disease processes.

“Advanced immune surveillance is a clue into how the immune system is attempting to restore balance and calm in the tissues,” Dr. Lo said. “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. 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.”

The research team is now focused on untangling the processes, potentially enabling the discovery of more selective therapies targeting TNF-alpha.