Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

This article is part of the supplement: 25th European Workshop for Rheumatology Research

Poster presentation

Active immunization (vaccination) against peptides of IL-1β induces self anti-IL-1β antibodies and protects against collagen-induced arthritis

N Bessis1, S Bertin-Maghit2, C Capini2, J Chomilier3, S Muller4, J-F Zagury2 and M-C Boissier1

Author Affiliations

1 Université Paris 13 UPRES EA3408 Bobigny and Avicenne AP-HP, Bobigny, France

2 Université Paris 6/INSERM EMI0355, Paris, France

3 Universités Paris 6 and Paris 4, Paris, France

4 UPR 9021 CNRS, IBMC, Strasbourg, France

For all author emails, please log on.

Arthritis Research & Therapy 2005, 7(Suppl 1):P137  doi:10.1186/ar1658

The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Objectives

IL-1β is a critical cytokine in inflammation and is involved in the pathogenesis of rheumatoid arthritis. Blocking IL-1β is efficient in the treatment of inflammation. Our goal was to inhibit inflammatory arthritis with a new approach consisting of targeting specific IL-1β peptides in the receptor binding site, and to prove this concept in an experimental model of arthritis.

Methods

Epitopes of IL-1β to be blocked were defined in silico by molecular modelling. Synthetized peptides (Fmoc strategy) were linked to KLH. Anti-IL-1β antibodies generated by vaccination of mice against each peptide coupled to KLH were tested by ELISA and neutralisation assay, determining their ability to inhibit IL-2 production by EL4/NOB1 cells. Collagen-induced arthritis (CIA) was induced in DBA/1 mice with type II collagen in complete Freund adjuvant. Mice were evaluated blindly for clinical arthritis, and joint histology was performed at sacrifice (60 days post-immunization with type II collagen). Mice were immunized by peptide conjugated to KLH 11 weeks prior to induction of CIA. Control groups received KLH alone or saline.

Results

Six peptides were obtained and were able to generate anti-IL-1β antibodies in mice (positive ELISA and neutralization assay). Three of them, chosen on the basis of the ability to generate the highest antibody response, were studied in CIA. One of them (IL-1β6) yielded a significantly improved resolution of CIA (P = 0.0003 as compared with KLH control, analysis of variance); the maximal arthritic score mean was also reduced in the treated group (9.4 ± 1.9 and 14.2 ± 1.7, P < 0.05). Histological analysis showed a clear-cut significant reduction in inflammation (P < 0.001) and destruction (P < 0.01) scores in the groups treated with IL-1β6.

Conclusion

Active immunization with targeted peptides of IL-1β was able to generate neutralizing anti-IL-1β auto-antibodies. Vaccination of mice with one of them, IL-1β6, was efficient in CIA.