Altered alveolar macrophage function in calorie-restricted rats

Am J Respir Cell Mol Biol. 1998 Sep;19(3):462-9. doi: 10.1165/ajrcmb.19.3.3114.


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.

MeSH terms

  • Animals
  • Cell Count / drug effects
  • Diet*
  • Inflammation / microbiology
  • Lipopolysaccharides / pharmacology
  • Lung / drug effects*
  • Macrophages, Alveolar / drug effects*
  • Male
  • Neutrophils / metabolism
  • Nitric Oxide / metabolism
  • Ozone / pharmacology
  • Phagocytosis / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred F344
  • Streptococcus / pathogenicity
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Lipopolysaccharides
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Ozone