Tumor necrosis factor-alpha and acute-phase proteins in early pregnant ewes after challenge with peptidoglycan-polysaccharide.
Bacterial infection shortly after mating interferes with establishment of pregnancy. Injection of peptidoglycan-polysaccharide (PG-PS), a component of gram-positive bacteria, into sheep on day 5 after mating reduces pregnancy rate. Experiments were designed to evaluate the acute-phase response (APR) in ewes to injection of PG-PS on day 5 after mating (day 0). Catheters were inserted into the jugular and posterior vena cava on day 4. On day 5, ewes were challenged with saline or 30 microg/kg body weight (BW) PG-PS (Exp 1) or 60 microg/kg BW PG-PS (Exp 2). Blood samples were collected every 15 min for 6 h (Exp 1) and every 15 min for 2 h, hourly for 12 h, and at 24, 36, and 48 h (Exp 2). Body temperature and clinical signs of infection were monitored in Exp 2. Plasma was assayed for concentrations of a pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha); 2 APR proteins, serum amyloid A (SAA) and haptoglobin (Hp); and progesterone (P(4)). Ewes injected with 60 microg/kg BW PG-PS exhibited fever, vaginal discharge, loss of appetite, and lethargy. After challenge with either 30 microg/kg or 60 microg/kg BW PG-PS, TNF-alpha increased in the posterior vena cava. Concentrations of SAA and Hp in the jugular increased after challenge with 60 microg/kg BW PG-PS. Only half (5/10) of the ewes treated with 60 microg/kg BW PG-PS had ultrasonically visible embryos, and none of them had functional corpora lutea (CL) (<1 ng/mL of P(4)) on day 21. On the other hand, 8/9 (88.9%) control ewes had visible embryos and all had functional CL on day 21. Using logistic regression, pregnancy on day 21 was predicted to depend on concentrations of TNF-alpha and Hp on day 5 and concentration of P(4) on day 14. In summary, injection of PG-PS on day 5 after mating resulted in fever; increased concentrations of TNF-alpha, Hp, and SAA on the day of and the day after the PG-PS challenge; and decreased concentrations of P(4) on days 14 and 21. These factors were related to failure to establish pregnancy.
Dow
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Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV 26506-6108, USA.
Rogers-Nieman
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Holásková
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Elsasser
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Dailey
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D000209:Acute-Phase Proteins / Q000276:immunology*; D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D003338:Corpus Luteum / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000097:blood / Q000276:immunology*; D006242:Haptoglobins / Q000276:immunology; D007113:Immunity, Innate; D010457:Peptidoglycan / Q000008:administration & dosage / Q000276:immunology*; D011134:Polysaccharides / Q000008:administration & dosage / Q000276:immunology; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000662:veterinary; D011270:Pregnancy, Animal / Q000276:immunology* / Q000502:physiology; D011374:Progesterone / Q000097:blood / Q000276:immunology; D000685:Serum Amyloid A Protein / Q000276:immunology; D012756:Sheep; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology*
D000209:Acute-Phase Proteins; D006242:Haptoglobins; D010457:Peptidoglycan; D011134:Polysaccharides; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone