The influence of restricted calorie intake on peritoneal macrophage function

Abstract

Malnutrition leads to immune dysfunction with greatly increased morbidity. However, restrictive dietary regimens are also known to preserve immune function in autoimmune-susceptible mice. The macrophage (M∅) is central to both immune effector and autoregulatory functions and is critical to host-defense mechanisms. The aim of this study was to investigate the effect of calorie restriction on M∅ functions in mice. Female, 6- to 8-wk-old, Swiss Webster mice were randomized to ad libitum feeding for 7 or 21 d ( n = 10 mice/group), restricted feeding (13.5 to 14.0 g/cage/d; n = 10) for 7 d, or restricted feeding (16.5 to 17.0 g/cage/d; n = 10) for 21 d. These restrictions were equivalent to a decrease in calorie intake of 21.9% and 5.1%, respectively, over 7 and 21 d. All mice were allowed free access to water. On days 8 and 22, respectively, the mice were killed, and peritoneal M∅s were isolated by lavage and adhered to 96-well polystyrene tissue-culture–treated plates. After stimulation with lipopolysaccharide, supernatant prostaglandin E 2 and interleukin-6 levels were measured by enzyme-linked immunosorbent assay. Supernatant NO 2 − in response to stimulation with lipopolysaccharide and interferon-γ was determined by the Greiss reaction. Prostaglandin E 2 production was significantly elevated in peritoneal M∅s from the calorie-restricted mice compared with the ad-libitum–fed mice after 7 d. After 21 d, production of both prostaglandin E 2 and nitric oxide was significantly increased ( P < 0.05) in peritoneal M∅s from the restricted mice compared with the ad-libitum–fed mice. These results indicate that calorie restriction influences immune function by altering prostaglandin E 2 and nitric oxide generation by M∅s.