Plasma cells and IL-4 in chronic bronchitis and chronic obstructive pulmonary disease.

Abstract

Airway wall inflammation, IL-4, and mucus hypersecretion are thought to be associated. To quantify bronchial inflammatory cells in smokers with chronic bronchitis (CB) with and without airflow obstruction (AO), determining the cells expressing IL-4 and IL-5 and their association with submucosal gland mucin. We applied immunohistochemistry to identify, and double-labeling to colocalize, IL-4 and IL-5 to distinct inflammatory cells in resected bronchi from (1) 11 asymptomatic smokers (AS), (2) 11 smokers with CB, and (3) 10 smokers with CB and AO. There were greater numbers of mucosal and gland CD45(+) leukocytes in CB (epithelium, 673/mm(2); subepithelium, 698/mm(2); gland, 517/mm(2)) than in AS (331, 237, and 178/mm(2), respectively; p < 0.01 for all) or CB + AO (375, 243, and 215/mm(2), respectively; p < 0.05 for all). There were greater numbers of subepithelial and submucosal gland plasma cells in CB (subepithelium, 110/mm(2); gland, 213/mm(2)) compared with AS (38 and 41/mm(2), respectively; p < 0.01 for both), and more subepithelial mast cells in CB (204/mm(2)) than in AS (65/mm(2); p < 0.01) or CB + AO (115/mm(2); p < 0.01). In CB, the percentage of gland occupied by mucin was positively correlated with the numbers of interstitial CD45(+) cells, plasma cells, and IL-4 protein(+) cells. In CB, 69 and 62% of gland-associated plasma cells expressed IL-4 and IL-5, respectively. Inflammatory cells are increased in bronchial submucosal glands and mucosa of large airways in smokers with CB. Gland-associated plasma cells express IL-4, and these likely promote mucus hypersecretion.