Newswise — Clinical and biochemical evidence points to eosinophils " a member of the white blood cell family " in connection with inflammatory reactions relative to asthma according to a summary of clinical data presented at the 61st Annual Meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in New Orleans.
William W. Busse, M.D., Charles E. Reed Professor of Medicine and Head, Allergy and Immunology, University of Wisconsin Medical School, Madison, Wis., kicked off the session accounting the clinical and biochemical evidence that points this cellular culprit's role in the underlying asthma disease process. Eosinophils deposit granules on the lung, infiltrate lung tissue, and send signals to recruit more inflammatory cells and to help eosinophils in the lung live longer. Asthma is a chronic inflammatory condition therefore bringing eosinophils under control is a potential therapeutic strategy that would address a root cause.
Eosinophils originate in the bone marrow and travel via the peripheral bloodstream to their target. Some of the critical steps involved in the process are dependent on a biochemical known as Interleukin -5 (IL-5). The signal had been identified as a possible Achilles Heel and it was thought that eliminating it out with a targeted therapy would produce a clinical benefit for patients. While the monoclonal antibody designed to interfere with IL-5 was quite effective at pairing down the number of eosinophils found in the blood and sputum, clinical trials failed to produce any remarkable clinical benefit. The results cast uncertainty over the eosinophil's viability as a therapeutic target. However, Dr. Busse invited Harald Renz, M.D., Philipps University Hospital, Marburg, Germany, and Patrick Flood-Page, M.D., London, UK, to discuss more recent evidence that suggests researchers may simply need to look further downstream and compartmentalize their thinking when it comes to the eosinophil.
By prolonging allergen challenges over months, Dr. Renz developed a murine model that mimics the persistent inflammation and airway remodeling observed in the more chronic stages of bronchial asthma. He noticed eosinophils accumulated in the lung mucosa of the peripheral airways only later on as the disease progressed in these animals. He also found that once in the mucosa, the eosinophils were received signals from other biochemicals present in the blood. His studies emphasized the need to study the immunobiology of eosinophils relative to the anatomical compartment.
Clinical data collected by Dr. Flood-Page further enforced the idea. He investigated the impact of inhibiting IL-5 on the process of tissue remodeling in human lung tissue. An anti-IL5 monoclonal depressed the number of eosinophils and those cells infiltrating the mucosa exhibited hindered the expression of two proteins (ie, tenascin and lumica) necessary to the tissue remodeling process. The two proteins are also often elevated in asthma patients. The relevance of Dr. Flood-Page's findings is unclear because the clinical relevance of remodeling is still unclear. Further understanding of these complex relationships should result in the identification of novel therapeutic targets needed to improve the treatment of asthma.
The ACAAI is a professional medical organization, headquartered in Arlington Heights, Ill., comprised of 4,963 qualified allergists-immunologists and related health care professionals. The College is dedicated to the clinical practice of allergy, asthma and immunology through education and research to promote the highest quality of patient care.
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