Association between protective efficacy of antibodies to tumor necrosis factor and suppression of nitric oxide production in neonatal rats with fatal infection.
In a rat model of fatal infection caused by Pseudomonas aeruginosa, the circulating level of nitrite/nitrate (NO2-/NO3-), a good indicator for nitric oxide production, was remarkably increased after elevation of circulatory tumor necrosis factor (TNF). Anti-TNF MAb cotreatment was shown to blunt hypoglycemia and hyperlacticemia and was associated with decreased mortality of septic animals. Moreover, anti-TNF MAb significantly reduced not only plasma TNF but also plasma NO2-/NO3- levels. Dexamethasone had a similar effects, and when anti-TNF MAb was used in combination with dexamethasone, the suppression of nitric oxide production and the protective efficacy were more remarkable compared with therapy with either anti-TNF MAb or dexamethasone alone. Our present data suggested that the protective efficacy of anti-TNF MAb may correlate with the suppression of nitric oxide production and also with a modulation in metabolic abnormalities in the septic newborn rats.
Shi
Y
Y
Department of Pediatrics, Daping Hospital, Chongqing, Sichuan Province, China.
Li
H Q
HQ
Shen
C K
CK
Wang
J H
JH
Pan
J
J
Qin
S W
SW
Liu
R
R
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016470:Bacteremia / Q000503:physiopathology / Q000628:therapy*; D003864:Depression, Chemical; D003907:Dexamethasone / Q000627:therapeutic use; D007518:Isoantibodies / Q000627:therapeutic use*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D011552:Pseudomonas Infections / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D019323:omega-N-Methylarginine
D007518:Isoantibodies; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine