Lofthouse S A, Andrews A E, Barcham G J, Nash A D
Centre for Animal Biotechnology, School of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
Vaccine. 1995 Oct;13(14):1277-87. doi: 10.1016/0264-410x(95)00074-b.
This paper describes aspects of the safety and efficacy of recombinant ovine interleukin-1 beta (rovIL-1 beta) as an immunological adjuvant. A dose-response relationship was established using the intramuscular route, and significant adjuvant activity was observed following delivery of 10 or 100 micrograms of the cytokine delivered either in PBS or in combination with alum. Similar doses of rovIL-1 beta also showed adjuvant activity when delivered via the subcutaneous route. In experiments in both mice and sheep, rovIL-1 beta-mediated adjuvant activity was neutralised by a monoclonal antibody (mAb), 3.41, confirming that the adjuvant effect was due to the biological activity of the cytokine. Serum clearance rates and physiological responses to intravenous, intramuscular or subcutaneous administration of rovIL-1 beta in sheep were also determined. RovIL-1 beta was shown to have a serum half-life of 2 min. Transient body temperature increases of 2 degrees C following intravenous or subcutaneous delivery, or 1 degrees C following intramuscular delivery, were observed. White blood cell counts also fluctuated post-injection, which was shown to be due to changes in the number of circulating neutrophils. The action of the neutralising mAb on serum clearance, body temperatures and white cell counts was also determined. Co-injection of rovIL-1 beta with the mAb 3.41 prevented rapid clearance of the cytokine from the serum, and was associated with an extension in elevated body temperature. The mAb appeared to have no significant influence on the white blood cell profile induced following injection with rovIL-1 beta.
本文描述了重组羊白细胞介素-1β（rovIL-1β）作为免疫佐剂的安全性和有效性方面。通过肌肉注射途径建立了剂量反应关系，当以10或100微克细胞因子（以PBS形式或与明矾联合）给药后，观察到显著的佐剂活性。当通过皮下途径给药时，相似剂量的rovIL-1β也显示出佐剂活性。在小鼠和绵羊实验中，rovIL-1β介导的佐剂活性被单克隆抗体（mAb）3.41中和，证实佐剂效应是由于细胞因子的生物活性。还测定了绵羊静脉内、肌肉内或皮下给予rovIL-1β后的血清清除率和生理反应。结果显示rovIL-1β的血清半衰期为2分钟。静脉内或皮下给药后体温短暂升高2℃，肌肉内给药后升高1℃。注射后白细胞计数也有波动，这被证明是由于循环中性粒细胞数量的变化。还测定了中和性单克隆抗体对血清清除率、体温和白细胞计数的作用。将rovIL-1β与单克隆抗体3.41共同注射可防止细胞因子从血清中快速清除，并与体温升高的持续时间延长有关。该单克隆抗体似乎对注射rovIL-1β后诱导的白细胞谱没有显著影响。
