Bovine recombinant interleukin-2 augments immunity and resistance to bovine herpesvirus infection☆

The in vivo administration of bovine recombinant interleukin-2 (rIL-2) was evaluated in calves vaccinated and then challenged with bovine herpesvirus-1 (BHV-1). In Experiment 1, 24 calves were allotted to four groups: control; bovine rIL-2; BHV-1 vaccine (modified-live); and bovine rIL-2+BHV-1 vaccine. Serum neutralizing antibody titers to BHV-1 were increased sixfold, and virus shedding was fourfold less in calves vaccinated and treated with rIL-2 (25 μg/kg, intramuscularly) when compared to calves that received vaccine only. Treatment with rIL-2 induced lymphokine-activated killer activity that was eliminated by pretreating effector cells with complement and a monoclonal antibody (B26A) specific for the sheep red blood cell receptor. The rIL-2 treatment in BHV-1-vaccinated calves increased the calves' ability to withstand a BHV-1 challenge. However, during treatment with rIL-2, calves developed diarrhea and mild fever that abated after IL-2 treatment was stopped. A second experiment was then conducted to determine a dose of rIL-2 that would enhance immunity to BHV-1 without causing adverse side effects. Twenty-five calves were allotted to five groups that received injections of rIL-2 at 0.0, 25.0, 2.5, 0.25, or 0.025 μg kg−1 day−1 for 5 days. All calves received a modified-live BHV-1 vaccine. Calves treated with 25.0 μg kg−1 day−1 showed similar adverse side effects as in the first experiment but all other calves were normal. Compared to control calves, those treated with 25.0, 2.5, and 0.25 μg kg−1 day−1 of rIL-2 had higher (P<0.05) serum antibody titers to BHV-1 and following challenge lower (P<0.05) BHV-1 titers in nasal secretions; additionally, clinical disease as evidenced by nasal and ocular discharge was less severe (P<0.05). In vitro cytotoxic responses against BHV-1-infected bovine kidney cells were increased (P<0.05) in calves treated with rIL-2 in a dose dependent manner. These data suggest that bovine rIL-2 at 2.5 to 0.25 μg/kg may be an effective adjuvant to immunization.