PARAMETERS RELATED TO THE APPLICATION OF RECOMBINANT OVINE INTERLEUKIN-1-BETA AS AN ADJUVANT

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 delive ry of 10 or 100 mu g of the cytokine delivered either in PBS or in com bination 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 neut ralised by a monoclonal antibody (mAb), 3.41, confirming that the adju vant effect was due to the biological activity of the cytokine. Serum clearance rates and physiological responses to intravenous, intramuscu lar 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 intrave nous 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 circu lating neutrophils. The action of the neutralising mAb on serum cleara nce, body temperatures and white cell counts was also determined. Go-i njection of rovIL-1 beta with the mAb 3.41 prevented rapid clearance o f the cytokine from the serum, and was associated with an extension in elevated body temperature. The mAb appeared to have no significant in fluence on the white blood cell profile induced following injection wi th rovIL-1 beta.