Reddy P G, Blecha F, Minocha H C, Anderson G A, Morrill J L, Fedorka-Cray P J, Baker P E
Department of Anatomy, Kansas State University, Manhattan 66056.
Vet Immunol Immunopathol. 1989 Nov 30;23(1-2):61-74. doi: 10.1016/0165-2427(89)90110-4.
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 micrograms/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 micrograms kg-1 day-1 for 5 days. All calves received a modified-live BHV-1 vaccine. Calves treated with 25.0 micrograms 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 micrograms kg-1 day-1 of rIL-2 had higher (P less than 0.05) serum antibody titers to BHV-1 and following challenge lower (P less than 0.05) BHV-1 titers in nasal secretions; additionally, clinical disease as evidenced by nasal and ocular discharge was less severe (P less than 0.05). In vitro cytotoxic responses against BHV-1-infected bovine kidney cells were increased (P less than 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 micrograms/kg may be an effective adjuvant to immunization.
对接种牛疱疹病毒1型（BHV-1）疫苗后再接受攻击的犊牛进行了牛重组白细胞介素-2（rIL-2）的体内给药评估。在实验1中，将24头犊牛分为四组：对照组；牛rIL-2组；BHV-1疫苗（减毒活疫苗）组；牛rIL-2+BHV-1疫苗组。与仅接种疫苗的犊牛相比，接种疫苗并用rIL-2（25微克/千克，肌肉注射）治疗的犊牛对BHV-1的血清中和抗体滴度提高了6倍，病毒排出量减少了4倍。rIL-2治疗诱导了淋巴因子激活的杀伤活性，用补体和针对绵羊红细胞受体的单克隆抗体（B26A）预处理效应细胞可消除这种活性。在接种BHV-1疫苗的犊牛中进行rIL-2治疗提高了犊牛抵抗BHV-1攻击的能力。然而，在rIL-2治疗期间，犊牛出现腹泻和轻度发热，在停止IL-2治疗后症状减轻。随后进行了第二项实验，以确定能增强对BHV-1的免疫力且不引起不良副作用的rIL-2剂量。将25头犊牛分为五组，分别接受0.0、25.0、2.5、0.25或0.025微克·千克-1·天-1的rIL-2注射，持续5天。所有犊牛都接种了减毒活BHV-1疫苗。用25.0微克·千克-1·天-1治疗的犊牛出现了与第一项实验中类似的不良副作用，但其他所有犊牛均正常。与对照犊牛相比，用25.0、2.5和0.25微克·千克-1·天-1的rIL-2治疗的犊牛对BHV-1的血清抗体滴度更高（P<0.05），在接受攻击后鼻分泌物中的BHV-1滴度更低（P<0.05）；此外，以鼻和眼分泌物为证据的临床疾病症状较轻（P<0.05）。用rIL-2治疗的犊牛对感染BHV-1的牛肾细胞的体外细胞毒性反应呈剂量依赖性增加（P<0.05）。这些数据表明，2.5至0.25微克/千克的牛rIL-2可能是一种有效的免疫佐剂。
