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Interleukin (IL)-13, a key mediator of Th2-mediated immunity, contributes to the pathogenesis of asthma and other pulmonary diseases via its ability to generate fibrosis, mucus metaplasia, eosinophilic inflammation, and airway hyperresponsiveness. In these studies, we compared surfactant accumulation in wild-type mice and mice in which IL-13 was overexpressed in the lung. When compared with littermate controls, transgenic animals showed alveolar type II cell hypertrophy under light and electron microscopy. Over time, their alveoli also filled with surfactant in a pulmonary alveolar proteinosis pattern. At the same time, prominent interstitial fibrosis occurs. Bronchoalveolar lavage fluid from these mice had a three- to sixfold increase in surfactant phospholipids. Surfactant proteins (SP)-A, -B, and -C showed two- to threefold increases, whereas SP-D increased 70-fold. These results indicate that IL-13 is a potent stimulator of surfactant phospholipid and surfactant accumulation in the lung. IL-13 may therefore play a central role in the broad range of chronic pulmonary conditions in which fibrosis, type II cell hypertrophy, and surfactant accumulation occur.

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ABSTRACT. Because of current interest in use of a com-used prophylactically to accelerate fetal lung maturation and bination of glucocorticoid and thyroid hormones for pre-prevent RDS in human newborns (2, 3) and in at least one vention of respiratory distress syndrome we examined the clinical study (4) thyroxine was also reported to be effective in effects of dexamethasone and triiodothyronine (T3), alone this regard. However, the findings in a recent multicenter study and in combination, on glycogen content and rates of fatty that glucocorticoids are not as efficacious in preventing RDS as acid and phosphatidylcholine synthesis in fetal rat lung. earlier believed and that its effects may be largely confined to The hormones were administered to the mothers on the 2 female infants (5) has led to interest in use of a combination of days before delivery on days 17-22 of gestation. Both glucocorticoids and thyroid hormone for prevention of RDS (6).hormones increased the rate of choline incorporation into Prior to such clinical use, however, it is desirable to have inforphosphatidylcholine, an index of surfactant synthesis, on mation on the interaction of these hormones in the acceleration day 20 just prior to the normal developmental surge but of lung maturation in animals. had no effect on this parameter on days 19, 21, or 22.Previous studies in animals have shown that a combination of There is a developmental increase in lung glycogen on days glucocorticoid and thyroid hormones is more effective than either 17-20 with a decrease thereafter and a developmental hormone alone in accelerating fetal lung maturation and stimuincrease in the rate of fatty acid synthesis between days 20 lating surfactant production. In a morphological study in the and 21. The increases in glycogen content and fatty acid fetal rat, Hitchcock (7) reported maximal acceleration of lung synthesis were accelerated by dexamethasone and pre-maturation when glucocorticoids and thyroxine were both presvented by T3 and when the hormones were administered ent. Similarly, a synergistic interaction between glucocorticoids together T3 antagonized the stimulatory effects of dexa-and thyroid hormone in stimulating synthesis of phosphatidylmethasone on these parameters. Both dexamethasone and choline and disaturated phosphatidylcholine, the major compo-T3 accelerated the normal developmental decrease in lung nent of pulmonary surfactant (I), was demonstrated in fetal rat glycogen later in gestation and the effects of the two lung in vivo (8,9) and in fetal rat (10, 1 I), rabbit (12), and hormones on this parameter were additive. The combina-human (1 3) lung in culture. tion of dexamethasone and T3 led to significantly smaller In addition to morphology and synthesis of surfactant phosfetuses and increased mortality late in gestation. These pholipids, lung maturation may also be assessed by other criteria. data show that glucocorticoid and thyroid hormones have An increase followed by a decrease in glycogen content is a opposite as well as common effects on...