Immune Dysfunction in Cystic Fibrosis

Abstract

Cystic Fibrosis (CF) is one of the most widespread life-shortening genetic diseases. CF is often diagnosed at birth; there is no cure, and many CF patients die from chronic lung disease at a young age. Patients with CF experience declining pulmonary function related to chronic airway infection, inflammation and scarring. While the mechanism connecting abnormal CFTR function to chronic bacterial infection and inflammation of the airway has not been fully elucidated, recent evidence suggests that CF patients may have defects in their mucosal immunity, resulting in a predisposition to infection and production of a disproportionate inflammatory response to microbial stimuli. Studies show increased cytokine expression in sputum and bronchoalveolar lavage fluid samples in CF patients. To determine if this is secondary to the chronic inflammatory environment of the lungs or innate to CF immune cells itself, leukocytes were isolated from peripheral blood and stimulated with LPS and compared to healthy donors. Our hypothesis is that there will be an increase in cytokine expression in blood leukocytes as well, with a further increase in expression after LPS stimulation. This will demonstrate that the chronic inflammatory response is inherent to the CF mutation itself, as blood is sterile and devoid of infection.