1. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha.
- Author
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Svenson M, Hansen MB, Thomsen AR, Diamant M, Nansen A, Rieneck K, Otterness IG, and Bendtzen K
- Subjects
- Animals, Autoantibodies blood, BCG Vaccine administration & dosage, Female, Humans, Immunity, Innate, Immunoglobulin G biosynthesis, Immunoglobulin G blood, Inflammation immunology, Interleukin-1 administration & dosage, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neutralization Tests, Receptors, Interleukin-1 metabolism, Recombinant Proteins administration & dosage, Recombinant Proteins immunology, Species Specificity, Vaccination, Autoantibodies biosynthesis, Immunization, Interleukin-1 immunology
- Abstract
High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding of IL-1alpha to the murine T-cell line NOB-1 by simple competition and neutralised IL-1alpha, but not IL-1beta-induced IL-6 in vivo. The aAb did not induce visible discomfort in the animals. In conclusion, long-lasting and high levels of neutralising and specific IgG aAb to IL-1alpha can be induced in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients with immunoinflammatory diseases and cytokine-dependent tumours.
- Published
- 2000
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