Effects of calorie restriction on polymicrobial peritonitis induced by cecum ligation and puncture in young C57BL/6 mice

Calorie restriction (CR) is known to prolong the life span and maintain an active immune function in aged mice, but it is still not known if rodents u nder CR can respond optimally to bacterial infection. We report here on the influence of CR on the response of peritoneal macrophages to lipopolysacch aride, splenic NF-kappaB and NF-interleukin-6 (IL-6) activities, and mortal ity in polymicrobial sepsis induced by cecal ligation and puncture (CLP). M acrophages from 6-month-old C57BL/6 mice on a calorie-restricted diet were less responsive to lipopolysaccharide, as evidenced by lower levels of IL-1 2 and IL-6 protein and mRNA expression. Furthermore, in vitro lipopolysacch aride-stimulated macrophages from mice under CR also expressed decreased li popolysaccharide receptor CD14 levels as well as Toll-like receptor 2 (TLR2 ) and TLR4 mRNA levels. In addition, the phagocytic capacity and class II ( I-A(b)) expression of macrophages were also found to be significantly lower in mice under CR. Mice under CR died earlier (P < 0.005) after sepsis indu ced by CLP, which appeared to be a result of increased levels in serum of t he proinflammatory cytokines tumor necrosis factor alpha and IL-6 and splen ic NF-<kappa>B and NF-IL-6 activation 4 h after CLP. However, mice under CR survived significantly (P < 0.005) longer than mice fed ad libitum when in jected with paraquat, a free radical-inducing agent. These data suggest tha t young mice under CR may be protected against oxidative stress but may hav e delayed maturation of macrophage function and increased susceptibility to bacterial infection.