Immune system protein may defend against deadly necrotizing enterocolitis in infants

Findings may lead to new therapies for necrotizing enterocolitis.

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Necrotizing enterocolitis, or NEC, is the most common and serious intestinal disease among premature babies. In this condition, bacteria invade the wall of the intestine. Inflammation sets in.

The disease causes tissue decay in the bowels. Once entered into the bloodstream, it can be more infectious and deadly.

Despite years of research, effective treatments remain elusive, and mortality rates remain unchanged.

A study by the Washington University School of Medicine in St. Louis has revealed a protein that may protect babies from necrotizing enterocolitis (NEC) and lead to the development of new treatments.

Interleukin-22 (IL-22) protein plays a vital role in regulating immune responses and maintaining a healthy gut microbiome in adults.

Scientists focused on Interleukin-22 (IL-22) protein in mice models. They studied the signaling and production of the protein in healthy intestines and intestines damaged by NEC. They analyzed IL-22 levels before and after birth and into adulthood, which for mice begins when they are weaned at about 28 days.

They analyzed IL-22 levels before and after birth and into adulthood, which for mice begins when they are weaned at about 28 days. In both healthy and diseased intestines, there was low postnatal IL-22 production IL-22 production up until day 21.

Scientists also studied tissue samples from preemies who did and did not develop NEC. They found low levels of IL-22 in all of the intestinal samples. In the babies who had developed NEC, an appropriate immune response had not been mounted in the intestines.

Misty Good, MD, assistant professor of pediatrics in the Division of Newborn Medicine, said, “Immune cells in the neonatal intestine have shown an inability to produce adequate amounts of IL-22 to control the progression of NEC. Immature intestines are associated with a lack of IL-22 production, a theory strengthened by the fact that premature infants weighing less than 3 pounds 5 ounces are most at risk for NEC.”

“Typically, the more premature a baby is, the lower the baby’s weight and the more undeveloped a baby’s gastrointestinal immune system is. Harmful bacteria can cross the gut barrier and activate the immune system. And because the immune system of preemies isn’t fully developed, it leads to an exaggerated inflammatory response that can lead to tissue death.”

Later, scientists injected the mice with IL-22. Doing so controlled the inflammation while promoting the regeneration of tightly packed cells lining the intestine.

 IL-22 can help strengthen the intestinal walls, creating a barrier in the gut that allows for nutrient absorption while preventing toxic or otherwise hostile microorganisms from seeping into the bloodstream.

Good said“Interestingly, our work demonstrated that treatment with IL-22, in mice, protects the newborn intestine against damage caused by NEC. Our study represents a substantial advance in understanding the role of IL-22 in early life and sets the stage for new ways to treat NEC in the future.”

Journal Reference:

  1. Belgacem Mihi et al. Interleukin-22 signaling attenuates necrotizing enterocolitis by promoting epithelial cell regeneration. Cell Reports Medicine, 2021; DOI: 10.1016/j.xcrm.2021.100320

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