Alveolar macrophage functions associated with clearance of bacteria from the lung were assessed in male Fischer 344 rats maintained on a 25%
calorie-restricted diet. Calorie-restricted and ad libitum-fed (control) rats were exposed to concentrations of
ozone known to compromise phagocytic function of alveolar macrophages.
Ozone suppressed alveolar macrophage phagocytosis of
latex beads in vitro in ad libitum-fed rats, but not in calorie-restricted rats. In fact,
caloric restriction enhanced phagocytic function in both control and
ozone-exposed animals. Ad libitum-fed rats exposed to
ozone and challenged with Streptococcus zooepidemicus experienced a prolonged
infection and influx of polymorphonuclear 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 macrophages isolated from calorie-restricted rats. Together, the data suggest that
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 pathophysiologic consequences.