Cytokine vaccination: neutralising IL-1 alpha autoantibodies induced by immunisation with homologous IL-1 alpha

High-affinity IgG autoantibodies (aAb) to IL-1 alpha are among the most fre quently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1 alpha, we immunised mice with recombinant murine IL-1 alpha. U nprimed and Bacille Calmette-Guerin (BCG)-primed BALB/cA mice were vaccinat ed with IL-1 alpha coupled to purified protein derivative of tuberculin (PP D). Both unprimed and primed animals developed IgG aAb to IL-1 alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1 beta. The induced anti-IL-1 alpha aAb inhi bited binding of IL-1 alpha to the murine T-cell line NOB-1 by simple compe tition and neutralised IL-1 alpha, but not IL-1 beta-induced IL-6 in vivo. The aAb did not induce visible discomfort in the animals. In conclusion, lo ng-lasting and high levels of neutralising and specific IgG aAb to IL-1 alp ha can be induced in mice by vaccination with recombinant murine IL-1 alpha conjugated to PPD. Studies of the effects of IL-1 alpha aAb in such animal s may help clarify the importance of naturally occurring IL-1 alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in p atients with immunoinflammatory diseases and cytokine-dependent tumours. (C ) 2000 Elsevier Science B.V. All rights reserved.