| Summary: | To determine the effects of zinc supplementation on the immune response to a combined viral-bacterial respiratory disease challenge, thirty-two beef heifers (255 ± 15 kg) were subjected to a 30-d period of Zn depletion, then randomly assigned to one of three treatment diets fed for 30 d before the challenge: (1) supplementation with 100 mg of Zn from Zn sulfate/kg of DM (Zn100), (2) supplementation with 200 mg of Zn from Zn sulfate/kg of DM (Zn200), and (3) supplementation with 80 mg of Zn/kg of DM from zinc methionine and 20 mg of Zn from Zn sulfate/kg of DM (ZinMet). After the 30-d supplementation period, all heifers were fitted with indwelling vaginal temperature (VT) devices and intra-nasally challenged with 1 × 10<sup>8</sup> PFU bovine herpesvirus-1 on d -3, and then allowed to rest in outdoor pens for 3 d. On d 0, each heifer was challenged intra-tracheally with an average dose of 2.38 × 10<sup>7</sup> CFU <i>Mannheimia haemolytica</i> (MH), fitted with an indwelling jugular catheter, and then moved into individual stalls in an environmentally-controlled enclosed barn. Whole blood samples were collected at 1-h (serum) and 2-h (complete blood counts) intervals from 0 to 8 h, and at 12, 24, 36, 48, 60, 72, 168, and 360 h relative to MH challenge. Data were analyzed using the MIXED procedure of SAS specific for repeated measures with fixed effects of treatment, time, and their interaction. There was a treatment effect (<i>p</i> < 0.01) for VT such that Zn200 heifers had greater VT than Zn100 and ZinMet heifers. There was a trend (<i>p</i> = 0.10) for a serum cortisol treatment effect with Zn100 heifers having greater cortisol than ZinMet heifers. Total leukocytes and lymphocytes were greater (<i>p</i> ≤ 0.01) in Zn100 heifers than Zn200 and ZinMet heifers, whereas monocytes were less (<i>p</i> = 0.05) in ZinMet heifers than Zn100 and Zn200 heifers. Concentrations of IL-6 were greater (<i>p</i> = 0.02) in ZinMet heifers than Zn100 and Zn200 heifers. Concentrations of IFN-γ were greater in Zn200 heifers than ZinMet heifers at 0 h, and Zn100 heifers from 0 to 12 h post-MH challenge (treatment x time <i>p</i> = 0.02). Serum haptoglobin was not affected by treatment or treatment x time (<i>p</i> ≥ 0.36) but increased over time (<i>p</i> < 0.01) in all groups. There was a trend (<i>p</i> = 0.11) for ZinMet heifers to have less severe nasal lesion scores than Zn100 heifers. The observed differential physiological responses in this study indicate that zinc source and concentration may alter the response to a bovine respiratory challenge in heifers.
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