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Researchers at the Stanley Manne Children's Research Institute of Ann & Robert H. Lurie Children's Hospital in Chicago have discovered a promising way to understand the development of necrotizing enterocolitis (NEC), a devastating bowel disease that commonly affects the premature, in order to treat it. By studying the early cellular events leading to NEC in a mouse model, they discovered that activation of a key protein (NF-κB transcription factor), which responds to stimuli such as bacterial products , triggers inflammation of the bowel before intestinal injury. Blocking NF-κB activity prevented the recruitment of bone marrow-derived monocytes (a type of white blood cell) into the gut and their subsequent differentiation into macrophages (immune cells involved in the inflammatory response but also in the unregulated tissue lesions). This process has decreased the development of NEC. Their conclusions were published in the American Journal of Pathology.
"Our study suggests a new potential NEC prevention strategy during the first few weeks of life for preterm babies at high risk of contracting the disease," said lead author Isabelle G. De Plaen, MD, neonatologist and researcher. at the Manne Research Institute. at Lurie Children's, who is also an badociate professor of pediatrics at the Feinberg School of Medicine at Northwestern University. "If we could intervene early to prevent excessive inflammation caused by monocyte recruitment before signs of NEC are detected, we could dramatically improve outcomes for these babies."
The inflammation is involved in the NEC and the damaged intestinal tissues often have to be removed surgically. The resulting short bowel is not always enough to ensure survival. Damaged intestinal tissue also allows bacteria normally confined in the intestinal cavity to infiltrate into the abdomen and cause an infection. This process can be overwhelming for a baby and may be fatal. The exact causes of NEC being unclear, no specific treatment is currently available and prevention remains a challenge.
"By investigating the first inflammatory events in NEC, we are getting a lot closer to developing ways to disrupt the mechanisms that contribute to this disease," says Dr. De Plaen.
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This study was funded in part by grants from the National Institutes of Health and funding from the Stanley Manne Children's Research Institute.
The research at Ann & Robert H. Lurie Children's Hospital in Chicago is conducted by the Stanley Manne Children's Research Institute. The Manne Research Institute strives to improve children's health, transform pediatric medicine, and build a healthier future through the never-ending quest for knowledge. Lurie Children's is ranked among the country's best children's hospitals in the U.S.News & World report. This is the pediatric training ground of the Feinberg School of Medicine at Northwestern University. Last year, the hospital served more than 212,000 children in 49 states and 51 countries.
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