The influence of restricted calorie intake on peritoneal macrophage function

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(null set)) 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(null set) functions in mice. Female, 6- to 8-wk-old, Swiss Webster mice were randomized to ad libitum feeding for 7 or 21 d (II = 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 2.1.9% 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(null set)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 NO2- ill response to stimulation with lipopolysaccharide and interferon-gamma was determined by the Greiss reaction. Prostaglandin E-2 production was significantly elevated in peritoneal M(null set)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(null set)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(null set)s. Nutrition 2001;17:41-45. (C)Elsevier Science Inc. 2001.