INTERLEUKIN-4 ALTERS EPITHELIAL-CELL DIFFERENTIATION AND SURFACTANT HOMEOSTASIS IN THE POSTNATAL MOUSE LUNG

Interleukin-4 (IL-4) is a pleotrophic cytokine which is increased duri ng lung injury and inflammation. Epithelial cell morphology and surfac tant homeostasis were assessed in 4-52-wk-old transgenic mice in which IL-4 was expressed in the bronchial and bronchiolar epithelial cells under the control of the Clara cell secretory protein promoter (CCSP-I L-4 mice), IL-4 caused progressive pulmonary infiltration with macroph ages, lymphocytes, neutrophils, and eosinophils. Epithelial cell hyper trophy and mucus cell metaplasia were observed in the lungs of CCSP-IL -4 mice at all ages, Airway epithelial cells contained increased neutr al glycoproteins and expressed gastric mucin, normally absent in the b ronchiolar epithelium of the mouse. Immunohistochemical and biochemica l studies demonstrated increased surfactant proteins A and B in lung s ections and lung homogenates of CCSP-IL-4 transgenic mice. Increased i mmunostaining for surfactant proprotein C was also detected in type II epithelial cells of the transgenic mice. In contrast, surfactant prot ein B and CCSP expression was decreased or was absent in hypertrophic epithelial cells lining the conducting airways of transgenic mice. Lun g-specific increase in T-cell proliferative responses to mitogenic sti mulation and antibody secretion were detected in CCSP-IL-4 mice. Diffe rentiated characteristics of respiratory epithelial cells were dramati cally influenced by the chronic production of IL-4 in the conducting a irways. Alterations in lung morphology in the CCSP-IL-4 mice are simil ar to some of those induced by antigenic stimulation or associated wit h chronic airway inflammation.