Interleukin‐4 and ‐13 expression is co‐localized to mast cells within the airway smooth muscle in asthma

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Abstract
Background Airway smooth muscle infiltration by mast cells is a feature of asthma and not eosinophilic bronchitis. In asthma, Th2 cytokines have been implicated as playing a critical role in the development of airway inflammation and hyper‐responsiveness. Whether inflammatory cells within the airway smooth muscle release these cytokines is unknown. Methods We have undertaken a comparative immunohistochemical study in bronchial biopsies from 14 subjects with asthma, 10 with eosinophilic bronchitis and eight normal controls recruited from two centres. Results The median number of IL‐4+ cells/mm2 smooth muscle was significantly higher in subjects with asthma than eosinophilic bronchitis and normal controls for both the anti‐IL‐4 mAb 3H4 (2.4, 0, 0, respectively; P=0.001) and anti‐IL‐4 mAb 4D9 (1.6, 0, 0, respectively; P=0.02). There were no group differences in the number of IL‐5+ cells (P=0.31). In six subjects with asthma, IL‐13 expression by cells within the airway smooth muscle was studied. The median (range) of IL‐13+cells was 2 (0.9–2.7). Ninety‐four percent of the cells expressing IL‐4 (3H4), 92% of those expressing IL‐4 (4D9) and 100% expressing IL‐13 in the airway smooth muscle were mast cells. Fifty‐five percent of the mast cells within the airway smooth muscle co‐localized to IL‐4 (3H4), 29% to IL‐4 (4D9) and 17% to IL‐13. Conclusions In asthma, IL‐4+ and IL‐13+ cells were present within the airway smooth muscle and were expressed predominantly by mast cells, suggesting that IL‐4 and IL‐13 may play an important role in mast cell–airway smooth muscle interactions.