Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

W Tang, GP Geba, T Zheng, P Ray… - The Journal of …, 1996 - Am Soc Clin Investig
W Tang, GP Geba, T Zheng, P Ray, RJ Homer, C Kuhn, RA Flavell, JA Elias
The Journal of clinical investigation, 1996Am Soc Clin Investig
Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to
respiratory viruses, cytokines, and histamine. To further define its potential effector functions,
the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the
resulting transgene mice were characterized. In contrast to transgene (-) littermates, the
airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell
infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory …
Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders.
The Journal of Clinical Investigation