Arginine Supplementation Induces Arginase Activity and Inhibits TNF‐α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction

Background: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor–α (TNF‐α) and interleukin‐10 (IL‐10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals. Material and Methods : Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham– /– (standard chow), IO and IO–/– (standard chow + IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF‐α and IL‐10 levels were analyzed in splenic macrophage cultures. Results : Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO –/– , and Arg–/– groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF‐α levels (Arg vs IO group, P < .05) and maintenance of IL‐10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines ( Sham –/–, IO–/–, and Arg–/– vs other, P < .05). Conclusions : Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF‐α levels, which may be directly related to nitric oxide derived from arginine.