Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha.
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.
Svenson
M
M
Institute for Inflammation Research, Rigshospitalet National University Hospital, Copenhagen, Denmark.
Hansen
M B
MB
Thomsen
A R
AR
Diamant
M
M
Nansen
A
A
Rieneck
K
K
Otterness
I G
IG
Bendtzen
K
K
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D001500:BCG Vaccine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007249:Inflammation / Q000276:immunology; D007375:Interleukin-1 / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013045:Species Specificity; D014611:Vaccination
D001323:Autoantibodies; D001500:BCG Vaccine; D007074:Immunoglobulin G; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins