Nutritional regulation of plasma tumor necrosis factor-alpha and plasma and urinary nitrite/nitrate responses to endotoxin in cattle.

Effects of dietary protein level with and without L-arginine (Arg) infusion on plasma tumor necrosis factor-alpha (TNF-alpha) response to endotoxin (lipopolysaccharide [LPS]) as well as plasma concentration and urine output of nitrite and nitrate (NOx), the stable end products of nitric oxide radical (NO), were studied in beef heifers (275-310 kg body wt). The animals were fed low- (LP; 7.96%) or high- (HP; 13.94%) protein diets for 10 days before LPS administration (Escherichia coli; 0.2 microgram/kg, iv). L-Arginine in saline (0.5 g/kg body wt) or saline was infused for 8 hr with one-third of total Arg infused before LPS administration. Plasma TNF-alpha concentrations increased in all heifers after LPS injection (peak at 1 hr and return to baseline at 4 hr); however, concentrations were lower in HP- than in LP-fed heifers at 1, 2, and 3 hr. Infusion of Arg did not affect plasma TNF-alpha response to LPS. Plasma NOx concentrations increased in all heifers after LPS challenge; compared with saline, Arg infusion increased the total response (integrated area under concentration curve) in LP- but not in HP-fed heifers. Relative to pretreatment period, the rate of NOx output in urine collected 2-6 hr after LPS administration increased in all heifers regardless of dietary protein level and was further amplified by Arg infusion. The rate of NOx output in urine collected 6-24 hr after LPS challenge was even higher in LP-fed heifers infused with Arg but returned to the basal values in other groups. Activity of hepatic inducible NO synthase was not affected by LPS, Arg, or dietary protein level at the time points studied. The data suggest that dietary protein levels can modulate both TNF-alpha and NO responses to LPS in cattle; high dietary protein intake decreases TNF-alpha response and attenuates the conversion of supplemental Arg to NO.