Am. J. Respir. Crit. Care Med., Volume 164, Number 12, December 2001, 2220-2228

Interleukin-4 and Interleukin-5 Gene Expression and Inflammation in the Mucus-secreting Glands and Subepithelial Tissue of Smokers with Chronic Bronchitis
Lack of Relationship with CD8⁺ Cells

JIE ZHU, SWATI MAJUMDAR, YUSHENG QIU, TAREQ ANSARI, ALESSANDRO OLIVA, JOHAN C. KIPS, ROMAIN A. PAUWELS, VIRGINIA DE ROSE, and PETER K. JEFFERY

Department of Gene Therapy, Imperial College School of Medicine, London, United Kingdom; Department of Clinical and Biological Sciences, University of Torino, Turin, Italy; and Department of Pathology, University Hospital, Ghent, Belgium

We wished to determine if the inflammatory cells surrounding the airway mucus-secreting glands in chronic bronchitis (CB) were associated with interleukin (IL)-4 and IL-5 mRNA expression and whether the CD8 T cell population expressed these cytokines. Digoxigenin-labeled IL-4 and IL-5 antisense RNA probes were used to detect gene expression in 11 asymptomic smokers (AS), 11 smokers with CB alone with normal lung function, and 10 smokers with chronic bronchitis and coexisting chronic obstructive pulmonary disease (CB+COPD; FEV₁% of predicted of 43-77% and FEV₁/ FVC of 51-68%). There were approximately three times as many IL-4 than IL-5 mRNA⁺ cells. The highest number of IL-4 mRNA⁺ cells were in the submucosal glands of the CB group with normal lung function (216/mm²), significantly higher than the values in either the AS (63/mm²) or the CB+COPD (87/mm²) groups, respectively (p < 0.01). There were similar group differences when the total numbers of inflammatory cells were compared. Accordingly, there was a positive correlation between the number of IL-4 mRNA⁺ cells and the total number of inflammatory cells in both the subepithelium and glandular compartments (r = 0.60; p = 0.01 and r = 0.70; p = 0.02, respectively). There were no significant associations between the numbers of CD8⁺ and IL-4 or IL-5 mRNA⁺ cells. Of 1328 IL-4⁺ and 1404 CD8⁺ cells counted none was double labeled. Of 727 IL-5⁺ and 1569 CD8⁺ cells, none was double labeled. In contrast, as a positive control, 34% of tumor necrosis factor (TNF)-⁺ cells were also CD8⁺ and 15% of CD8⁺ cells were TNF- positive. Thus, cells other than the CD8⁺ phenotype produce IL-4 and IL-5 in CB. We conclude that there is increased inflammation and IL-4 gene expression in the mucus-secreting glands and the airway mucosa of smokers with bronchitis: both are lower in those with CB and coexisting COPD suggesting that airway inflammation in CB is reduced when airway obstruction develops.

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