Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: lymphocytic and eosinophilic inflammation without airway …

JA Rankin, DE Picarella, GP Geba… - Proceedings of the …, 1996 - National Acad Sciences
JA Rankin, DE Picarella, GP Geba, UA Temann, B Prasad, B DiCosmo, A Tarallo, B Stripp
Proceedings of the National Academy of Sciences, 1996National Acad Sciences
To investigate the contribution of interleukin-4 (IL-4) to airway inflammation in vivo and to
explore directly its relationship to airway reactivity, we created transgenic mice in which the
murine cDNA for IL-4 was regulated by the rat Clara cell 10 protein promoter. Expression
was detected only in the lung and not in thymus, heart, liver, spleen, kidney, or uterus. The
expression of IL-4 elicited hypertrophy of epithelial cells of the trachea, bronchi, and
bronchioles. Hypertrophy is due, at least in part, to the accumulation of mucus glycoprotein …
To investigate the contribution of interleukin-4 (IL-4) to airway inflammation in vivo and to explore directly its relationship to airway reactivity, we created transgenic mice in which the murine cDNA for IL-4 was regulated by the rat Clara cell 10 protein promoter. Expression was detected only in the lung and not in thymus, heart, liver, spleen, kidney, or uterus. The expression of IL-4 elicited hypertrophy of epithelial cells of the trachea, bronchi, and bronchioles. Hypertrophy is due, at least in part, to the accumulation of mucus glycoprotein. Histologic examination of parenchyma revealed multinucleated macrophages and occasional islands of cells consisting largely of eosinophils or lymphocytes. Analysis of lung lavage fluid revealed the presence of a leukocytic infiltrate consisting of lymphocytes, neutrophils and eosinophils. Mice expressing IL-4 had greater baseline airway resistance but did not demonstrate hyperreactivity to methacholine. Thus, the expression of IL-4 selectively within the lung elicits an inflammatory response characterized by epithelial cell hypertrophy, and the accumulation of macrophages, lymphocytes, eosinophils, and neutrophils without resulting in an alteration in airway reactivity to inhaled methacholine.
National Acad Sciences