Airway hyperresponsiveness and airway obstruction in transgenic mice morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung

Understanding the sources of variation in airway reactivity and airflow is important for unraveling the pathophysiology of asthma, obstructive lung di sease, and other pulmonary disorders. Transgenic expression of two closely related cytokines in the mouse lung produced opposite effects on these para meters. Interleukin (IL)-6 did not alter basal airways resistance and decre ased methacholine responsiveness, whereas IL-11 caused airways obstruction and increased airway responses to methacholine. To clarify these difference s we examined histologic sections and used morphometry to compare bronchiol ar and parenchymal dimensions in 1- to 2-mo-old transgenic mice expressing IL-6 or IL-11 and littermate control mice. Both transgenic strains showed s imilar emphysema-like airspace enlargement, nodular peribronchiolar collect ions of mononuclear cells, thickening of airway walls, and subepithelial ai rway fibrosis. When compared with littermate control mice, the IL-6 mice sh owed an approximately 50% increase in the caliber of their bronchioles and an increase in airway wall thickness that was in proportion to the increase in the size of their airways. In contrast, the remodeling response was mor e robust in the IL-11 transgenic mice. It was also seen in airways with nor mal external and luminal diameters and thus was out of proportion to the ca liber of their airways. These results support the hypothesis that structura l alterations and resulting caliber changes of respiratory airways can have important effects on airway physiology and reactivity.