Scientists at Children's Hospital of Pittsburgh of UPMC have identified a protein that is critical to the development of inflammation during lung infection in patients with cystic fibrosis (CF). The identification of this protein, called interleukin-23 (IL-23), is an important finding that gives researchers a specific target for developing new therapies.
In June 2005, Children's and University of Pittsburgh researchers led by Children's pulmonologist and immunologist Jay K. Kolls, MD, reported that IL-23 and another cytokine, interleukin-17, are elevated in CF patients with chronic lung infections. The latest research by Dr. Kolls and Children's pulmonologist Patricia Dubin, MD, pinpoints IL-23 as the crucial mediator to this inflammatory response. Results of this study are now published online in the American Journal of Physiology-Lung Cellular and Molecular Physiology.
Many patients with CF develop chronic lung infections from a strain of bacteria known as Pseudomonas aeruginosa. During chronic infection, the inflammatory response is never "shut off", and the continuous inflammation, mediated by IL-23 and other cytokines, may eventually lead to lung damage.
"Understanding the role IL-23 plays in the inflammatory pathway of CF patients is a major step forward that could lead to the development of new therapies to block this inflammation," said Dr. Kolls, chief of the Division of Pulmonary Medicine, Allergy and Immunology at Children's and professor of Pediatrics and Immunology at the University of Pittsburgh School of Medicine. "For patients with chronic infections associated with CF, this eventually could mean a prolonged life span and an improved quality of life."
Examining IL-23's importance in the inflammation pathway is a "new and different" approach than that taken by other CF researchers, according to Dr. Dubin, an assistant professor of Pediatrics at the University of Pittsburgh School of Medicine. "Currently, the anti-inflammatory therapies that we have for CF patients, steroids and non-steroidal anti-inflammatory drugs, are non-specific and can cause debilitating side effects such as the exacerbation of diabetes and glucose intolerance, as well as bone loss. The identification of specific inflammatory mediators like IL-23 opens the door to developing targeted anti-inflammatory treatments which may have fewer side effects."
CF is an inherited disease characterized by an abnormality in the body's salt-, water- and mucus-making cells. It is chronic, progressive and life-shortening. About 30,000 people in the United States have CF and about 1,000 babies are born with it each year. The life expectancy of a child born with CF is 36.5 years. The Antonio J. and Janet Palumbo CF Center at Children's follows more than 430 patients.
Children with CF have an abnormality in the function of a cell protein called the cystic fibrosis transmembrane regulator. This affects the flow of water and certain salts in and out of the body's cells, leading to the production of abnormally thick mucus. The thickened mucus can affect many organs and body systems, including the sinuses and lungs, pancreas, liver, gallbladder, intestines, and reproductive and sweat glands. In the sinuses and lungs, this thickened mucus allows bacteria that would normally be cleared from the airways to multiply and cause chronic infection.
Marc Lukasiak | EurekAlert!
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