ALTERED ALVEOLAR MACROPHAGE FUNCTION IN CALORIE-RESTRICTED RATS

Alveolar macrophage functions associated with clearance of bacteria fr om the lung were assessed in male Fischer 344 rats maintained on a 25% calorie-restricted diet. Calorie-restricted and nd libitum-fed (contr ol) rats were exposed to concentrations of ozone known to compromise p hagocytic function of alveolar macrophages. Ozone suppressed alveolar macrophage phagocytosis of latex beads in vitro in nd libitum-fed rats , but not in calorie-restricted rats. In fact, caloric restriction enh anced phagocytic function in both control and ozone-exposed animals. A d libitum-fed rats exposed to ozone and challenged with Streptococcus zooepidemicus experienced a prolonged infection and influx of polymorp honuclear leukocytes (PMN), whereas calorie-restricted rats exposed to ozone cleared the bacteria in 24 h without an inflammatory response. Bacterial endotoxin-stimulated in vitro production of nitric oxide and tumor necrosis factor (TNF)-alpha as well as expression of TNF-alpha and interleukin-6 messenger RNAs were all lower in alveolar macrophage s isolated from calorie-restricted rats. Together, the data suggest th at caloric restriction enhances resistance to gram-positive bacteria, while lowering the production of proinflammatory mediators elicited by endotoxin, a component of gram-negative bacteria. Although increased bacterial resistance is considered beneficial, reduction in the lung's ability to induce inflammatory mediators can have both positive and p athophysiologic consequences.