Effects of recombinant bovine interleukin-8 (rbIL-8) treatment on health, metabolism, and lactation performance in Holstein cattle III: Administration of rbIL-8 induces insulin resistance in bull calves.

Our previous work has suggested that recombinant bovine interleukin-8 (rbIL-8) treatment might influence cow metabolism. Therefore, this study was conducted to initially assess the effects of systemic administration of rbIL-8 on response to a glucose challenge, blood metabolites, insulin, growth hormone, insulin-like growth factor-1, immune cell populations, and inflammatory parameters in Holstein bull calves. Calves from 30 ± 6 d of life were individually housed and randomly allocated to 1 of 2 treatment groups: rbIL-8 (rbIL-8, n = 10) and control (CTR, n = 8). Calves assigned to the rbIL-8 group received 1 s.c. injection (d 1, 0900 h) and 6 i.v. injections (d 1 at 1600 h, d 2 and 3 at 0900 h and 1600 h, and d 4 at 0900 h) of rbIL-8 (4 μg/kg of body weight), whereas the CTR group received 2 mL of sterile saline solution at each time point. Day of enrollment was considered as d 1, and the study duration was 10 d. Insulin concentrations and whole-body glucose disappearance were evaluated by an i.v. glucose tolerance test conducted at 12 h and 7 d following the last rbIL-8 injection. Rectal temperature and blood samples were collected on d 1, 2, 3, and 4 at −30 (before treatment, 0830 h), 30, 60, 120, 240, and 360 min relative to treatment, and daily at 0830 h for the rest of the study period. Serum was harvested, and the following parameters were measured: β-hydroxybutyrate (BHB), nonesterified fatty acids, glucose, insulin, plasma urea nitrogen, haptoglobin, and differential blood count. Significant differences were considered when P ≤ 0.05 and a trend if 0.05 < P ≤ 0.10. Serum glucose levels and glucose area under the curve (AUC) did not differ between treatment groups in response to the glucose challenge. However, calves treated with rbIL-8 had greater serum insulin concentration and insulin AUC compared with controls. Administration of rbIL-8 increased rectal temperature (rbIL-8 = 39.3 ± 0.1; CTR = 38.9 ± 0.1°C; ±standard error), BHB concentrations (rbIL-8 = 3.54 ± 0.10; CTR = 2.99 ± 0.12 mg/dL), counts of lymphocytes (rbIL-8 = 4.52 ± 0.12; CTR = 3.84 ± 0.14 × 103/μL), monocytes (rbIL-8 = 0.87 ± 0.03; CTR = 0.67 ± 0.04 × 103/μL), and granulocytes (rbIL-8 = 3.54 ± 0.22; CTR = 2.66 ± 0.24 × 103/μL). We conclude that rbIL-8 induces insulin resistance in Holstein bull calves, accompanied by systemic inflammation and altered blood metabolites and white blood cell populations.