NUTRITIONAL REGULATION OF TNF AND PLASMA AND URINARY CONCENTRATIONS OF NITRITE/NITRATE RESPONSE TO ENDOTOXIN IN CATTLE

Authors: KAHL, STANISLAW - UNIVERSITY OF MARYLAND; Elsasser, Theodore; BLUM, JURG - UNIVERSITY OF BERNE

Submitted to: American Society for Experimental Biology and Medicine Proceedings
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/5/1997
Publication Date: N/A
Citation: N/A

Interpretive Summary: It is recognized that nutrition affects the ability of animals to resist disease. We studied this in cattle and designed an experiment to test if altering diet protein could affect two markers of immune response, tumor necrosis factor (TNF) and nitric oxide (NO) measured by changes in nitrate and nitrite in blood and urine. We fwd cattle two levels of protein that could affect metabolism by changing some lever enzymes that make urea from an amino acid called arginine. We gave the cattle a simulated bacterial cell compound called endotoxin to initiate immune response without actually having to infect the cattle with any bacteria. We measured the TNF and nitrite and nitrate and saw that the change in the immune response TNF and nitrate was lower in animals fed high protein. Sometimes the distress that animals feel during a disease results from too much of a good thing, ie., the immune system transiently produced too much TNF and NO. This study suggests that a high protein diet might be effective in reducing the severity of diseases because the overproduction of TNF and NO are limited.

Technical Abstract: Effects of dietary protein level with and without arginine infusion on plasma TNF response to endotoxin as well as plasma and urine concentration and output or nitrite/nitrate, the stable endproduct of nitric oxide radical (NO), were studied in beef heifers. The animals were fed low (LP, 8%) or high (HP, 14%) protein diets for 10 days before endotoxin administration (E, Coli, 055:B5, 0.2 ug/kg, iv). L-arginine in saline ().5 g/kg BW) or saline was infused for 8 hours with 1/3 of the total arginine infused before endotoxin. Plasma TNF concentrations, measured by RIA, increased in all heifers after endotoxin (peak at 1 hour and return to baseline by 4 hours), however, concentrations were lower in LP than in HP fed heifers at 1, 2 and 3 hours. Infusion of arginine did not affect TNF responses in plasma. Plasma nitrite/nitrate concentrations increased in all heifers after endotoxin; compared with saline, arginine infusion increased the total response (integrated area under the concentration-time curve) in LP but not in HP fed animals. Relative to pretreatment period, the rate of nitrite/nitrate output in urine collected 2 to 6 hours after endotoxin increased in all animals regardless of diet protein level and was amplified by arginine infusion. Activity of inducible NO synthase (iNOS) was not affected by LPS, arginine or diet. The data suggest that dietary protein can modulate both TNF and NO responses to endotoxin in cattle; high protein in diets decreases TNF response and attenuates the ability of arginine to promote NO synthesis.