Necrotizing enterocolitis is a significant cause of mortality among preterm children born in the United States and across the world. The illness, which is characterized by severe inflammation that can cause tissue breakdown in the intestines, offers a channel for infectious and lethal germs to enter the circulation.
In Newborns, An Immune System Protein May Protect Them From Potentially Fatal Intestinal Illness
Despite four decades of study, effective therapies are still elusive, and death rates in newborns with the illness have remained practically constant, hovering around 30%.
Meanwhile, researchers at Washington School of Medicine University, St. Louis have found a protein in the immune system that may protect infants against necrotizing enterocolitis (NEC) and lead to the development of novel therapies in mice.
Cell Reports Medicine published the findings online on June 15th.
According to the study’s principal author, Misty Good, MD, an associate professor of pediatrics in the Division of Newborn Medicine, necrotizing enterocolitis is a severe, fast-acting disease that can result in death within hours. Doctors don’t know why NEC occurs, and they can try to treat it with medicines and surgical removal of dead tissue; nevertheless, many babies will still die in severe instances. There are no therapies that stop the illness from advancing, but they are hopeful that the protein they have found will.
The researchers concentrated on Interleukin-22 (IL-22), a protein that controls immune responses and aids in the maintenance of healthy gut microbiota in adults.
IL-22 appears to have an important role in adult gastrointestinal disorders, according to studies.
As a result, possible IL-22-based therapies are being investigated in COVID-19 sickness, alcohol-induced liver disease, and graft-versus-host disease that occur following organ or bone marrow transplants. However, the role of IL-22 in the intestines of neonates is unknown.
To further understand the protein’s involvement, the researchers developed a mouse model to study IL-22 signaling and synthesis in healthy and NEC-damaged intestines. They looked at IL-22 levels before, during, and after birth, as well as during maturity, which for mice occurs when they are weaned, at around 28 days old. The researchers observed minimal postnatal IL-22 production in both healthy and sick intestines until day 21 when production surged for the mice and persisted throughout adulthood.
The researchers also examined tissue samples from preemies who had NEC and those who did not. The researchers discovered modest amounts of IL-22 in all of the intestinal samples. In addition, an adequate immune response had not been established in the intestines of the newborns who had had NEC.
According to Good, who serves patients at St. Louis Children’s Hospital and is also co-program director of the university’s Newborn-Perinatal Medicine Fellowship, immune cells in the neonatal gut have shown an inability to produce enough levels of IL-22 to limit the course of NEC. As a member of the Necrotizing Enterocolitis Society’s scientific advisory board, Good has spearheaded an initiative combining seven medical facilities to create a large biorepository of samples from NEC-affected newborns.
Good hypothesized that immature intestines are related to a lack of IL-22 production, a notion that is supported by the fact that preterm babies weighing less than 3 pounds 5 ounces are most vulnerable to NEC. The more preterm a newborn is, the lower the infant’s weight and the less developed the baby’s gastrointestinal immune system is. Bacterial pathogens can get through the intestinal barrier and stimulate the immune system. Because preemies’ immune systems aren’t completely matured, this causes an increased inflammatory response that can result in tissue death.
The researchers’ discovery of low amounts of IL-22 in newborn tissues prompted them to proceed to the next step: injecting the mice with IL-22. The protein helps to regulate inflammation while also encouraging regeneration of the intestine’s densely packed cells. IL-22 can help strengthen the intestinal walls, forming a barrier that allows nutrients to be absorbed while preventing poisonous or otherwise harmful bacteria from entering the circulation.
Interestingly, their research found that treating mice with IL-22 protects the neonatal gut against NEC damage, according to Good. The discovery marks a significant breakthrough in understanding the role of IL-22 in early life and lays the groundwork for novel approaches to treating NEC in the future.