ARS | Publication request: TUMOR NECROSIS FACTOR-ALPHA (TNF-ALPHA), NITRIC OXIDE (NO), AND XANTHINE OXIDASE (XO) RESPONSES TO ENDOTOXIN (LPS) CHALLENGE IN HEIFERS: EFFECT OF ESTROUS CYCLE PHASE

Submitted to: American Society of Animal Science
Publication Type: Abstract Only
Publication Acceptance Date: April 22, 2005
Publication Date: July 1, 2005
Citation: Kahl, S., Elsasser, T.H. 2005. Tumor necrosis factor-a, nitric oxide and xanthine oxidase responses to endotoxin (LPS) in heifers: effects of estrus cycle phase [abstract]. Journal of Animal Science. 83(Suppl 1):8.

Technical Abstract: The severity of host response in some diseases differs between sexes and this dimorphism has been attributed to the immunomodulating effects of steroid hormones. In females, puberty, pregnancy, menopause, and age have been shown to affect the immune response to a disease stress through the prevailing sex steroid milieu. Our objective was to determine in heifers whether the phase of estrous cycle affected the plasma concentration changes of immune response mediators after LPS challenge (2.5 µg/kg BW, i.v., E. coli 055:B5). Sixteen beef heifers (426 ± 9 kg) were synchronized to a similar stage of the estrous cycle with the two-injection protocol of dinoprost tromethamine (Lutalyse, Pfizer). Heifers were challenged with LPS 3 d (E, estrus; n = 8) or 10 d (D, diestrus) after the last i.m. injection of Lutalyse. Blood samples were collected at 0, 1, 2, 3, 4, 7, and 24 h after LPS injection. Plasma progesterone (P4) concentrations before LPS challenge (0 h) were 0.3 ± 0.1 and 4.2 ± 0.6 ng/mL in E and D, respectively. In all heifers, plasma TNF-' peaked 2 h after LPS (P< 0.01) and returned to basal level by 7 h. With TNF-' concentrations higher (P < 0.01) in E than D at the 1, 2, and 3 h samplings, the integrated TNF-' response (area under the time × concentration curve, AUC) was greater in E than in D (27.1 vs. 16.8 ng/mL × h, P < 0.05). Plasma concentrations of nitrate+nitrite (NOx), an estimate of NO production, and XO activity, a mediator of superoxide production, were measured. NOx increased (P < 0.01) in all heifers at 7 and 24 h after LPS; plasma NOx AUC after LPS was greater in E than D (146 vs. 65 µM × h, P < 0.01). Plasma XO responses were also greater in E than D (235 vs. 150 mU/mL × h, P < 0.05). Results indicate that the estrous cycle phase is a major source of variability in the magnitude of immune response to bacterial toxins like LPS. The discrimination in responses between cycle phases may reside in the prevailing P4 concentrations at the time of challenge encounter.