Effects of exogenous recombinant ovine interferon tau on circulating concentrations of progesterone, cortisol, luteinizing hormone, and antiviral activity; interestrous interval; rectal temperature; and uterine response to oxytocin in cyclic ewes

Interferon tau (IFNτ) is the conceptus-produced antiluteolytic signal in ruminants. Three experiments examined the effects of s.c. administration of recombinant ovine (ro)IFNτ on interestrous interval (IEI), oxytocin (OT)- induced uterine prostaglandin F(2α) metabolite (PGFM) production, rectal temperature (RT), respiration rate (RR), and plasma concentrations of progesterone, cortisol, LH, and antiviral activity (AVA) in plasma and uterine flushings. In experiment 1, 20 ewes were treated s.c. with either 0, 1, 2, or 4 mg/day roIFNτ (0.7 x 10⁸ U/mg; 5 ewes/dosage) from Days 11 to 15 of the estrous cycle (estrus = Day 0) and were challenged with OT (30 IU) on Day 15. Jugular blood samples were collected at -10, 0, 10, 20, 30, 40, 50, and 60 min relative to the OT challenge and assayed for PGFM. Recombinant oIFNτ increased IEI (16.7, 18.7, and 22.6 ± 0.6 days for 0, 2, and 4 mg roIFNτ, respectively, p < 0.01). Recombinant oIFNτ did not affect peak PGFM response to OT (2309 ± 172 pg/ml; p > 0.1). However, the 4 mg/day dosage delayed the time to peak PGFM (32.4 vs. 47.5 ± 3.4 min; p < 0.01, 0 vs. 4 mg) and resulted in approximately 200% higher concentrations of PGFM at 60 min post. OT (0 vs. 4 mg/day, p < 0.07). Experiment II was similar to experiment 1, except that only the 0- and 4-mg/day dosages of roIFNτ were administered. Ewes were hysterectomized on Day 16, and assay of uterine flushes detected no AVA from ewes treated with either 0 or 4 mg/day roIFNτ. In experiment III, 20 ewes were treated s.c. with either 0, 2, 4, or 6 mg roIFNτ on Day 12. Blood samples, RT, and RR were obtained at frequent intervals for 24 h, and plasma was assayed for progesterone, cortisol, LH, and AVA. Plasma AVA, which increased in a dose-dependent manner, was detectable within 60 min and remained elevated at 24 h compared to control values. RT (elevated 0.5-1.0°C), RR, and cortisol increased in response to all dosages of roIFNτ, with peak values occurring 150-180 rain postinjection. For all dosages of roIFNτ, plasma progesterone declined from 120 to 360 min posttreatment and then returned to pretreatment values by 24 h (p < 0.01) as compared to controls. Overall, exogenous roIFNτ altered uterine PGFM response to OT from a pulse to a gradual and sustained elevation and extended lEl with only a transient decline in progesterone and mild hyperthermia, effects that are not expected to compromise pregnancy.