Chronic oral administration of dexamethasone to rats increases cytotoxicity, but not interleukin-1 elaboration, by alveolar macrophages

Abstract

Chronic administration of corticosteroids has been used to induce pulmonary infection in animals. but the specific mechanisms by which corticosteroids modulate pulmonary host defence have not been clarified. Specifically, little is known about how corticosteroids influence the function of lung cells, such as alveolar macrophages. Cytotoxicity and interleukin-1 elaboration are two important mechanisms of macrophage defence against pathogens. To determine whether chronic administration of dexamethasone alters cytotoxicity and interleukin-1 elaboration by alveolar macrophages, we studied alveolar macrophages from rats treated with oral doses of dexamethasone for 2 weeks. We found that unstimulated alveolar macrophages from dexamethasone-treated rats exhibited increased cytotoxicity compared with alveolar macrophages from control rats. Moreover, alveolar macrophages from both groups of rats showed enhanced cytotoxicity after in vitro interferon-gamma and lipopolysaccharide treatment, in a dose-dependent manner. Although no spontaneous interleukin-1 elaboration was detected from alveolar macrophages from either group of rats, lipopolysaccharide increased interleukin-1 elaboration by alveolar macrophages from both groups of rats equivalently. These results indicate that chronic oral administration of dexamethasone to rats increases cytotoxicity, and does not alter the capacity of alveolar macrophages to elaborate interleukin-1. Therefore, chronic corticosteroid administration appears to produce selective alterations in these defence mechanisms of alveolar macrophages.