title: Estradiol plus progesterone treatment modulates select elements of the proinflammatory cytokine cascade in steers: attenuated nitric oxide and thromboxane B2 production in endotoxemia.
abstract: Estradiol plus progesterone (EP) implants have been shown to favorably alter the time course or decrease the severity of many of the clinical manifestations associated with coccidiosis and endotoxemia in calves. This study evaluated the effect of EP treatment on plasma tumor necrosis factor-alpha (TNF), thromboxane (TXB), prostacyclin (PRC), nitrite and nitrate (NO[x]), and cortisol. Holstein steer calves were divided into four groups: control, EP, endotoxin (LPS), and EP + LPS (n = five/group). Estradiol/progesterone pellets (Synovex-S) were implanted subcutaneously when calves reached 20 wk of age. One week after implantation, calves were injected i.v. with endotoxin (i.e., lipopolysaccharide; LPS, 0.6 microgram/kg of BW) or nonpyrogenic saline placebo. Body temperature was measured and blood was collected before injection and at 1, 2, 3, 4, 6, and 8 h thereafter. Plasma concentrations of TNF, cortisol, TXB, PRC, NO[x], were measured. Body temperature increased in both LPS and LPS-EP calves, but had returned to normal by 6 h in the LPS-EP group (P < 0.05). Plasma TNF and cortisol increased after LPS (P < 0.01), but were not differentially affected by EP treatment. Likewise, EP did not affect the magnitude of increase in LPS-induced PRC, but EP decreased the magnitude of increase in TXB (P < 0.05). Plasma NO[x]) levels were increased (P < 0.01) in calves after LPS; treatment with EP attenuated the LPS-associated increase in plasma NO[x] levels. These results suggest that EP exerts specific effects on different components of the proinflammatory cytokine cascade. Although the initiation of responses mediated by TNF, cortisol, and PRC do not seem to be differentially affected by EP, components of the nitric oxide- and TXB-axis responses to LPS are decreased in calves pretreated with EP.
authors.affiliation: Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849-5520, USA. sartijl@vetmed.auburn.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Sartin
authors.forename: T H
authors.initials: TH
authors.lastname: Elsasser
authors.forename: S
authors.initials: S
authors.lastname: Kahl
authors.forename: J
authors.initials: J
authors.lastname: Baker
authors.forename: J A
authors.initials: JA
authors.lastname: Daniel
authors.forename: D D
authors.initials: DD
authors.lastname: Schwartz
authors.forename: B
authors.initials: B
authors.lastname: Steele
authors.forename: B K
authors.initials: BK
authors.lastname: Whitlock
mesh_terms: D000821:Animal Feed / Q000633:toxicity; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D019446:Endotoxemia / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*; D004958:Estradiol / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D011374:Progesterone / Q000494:pharmacology*; D011897:Random Allocation; D013929:Thromboxane B2 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol; D013929:Thromboxane B2