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

Bessis, N ., Bertin-Maghit, S., Capini, C., Chomilier, J., Muller, S., Zagury, J.F. and Boissier, M.C. (2005) Active immunization (vaccination) against peptides of IL-1beta induces self anti-IL-1beta antibodies and protects against collagen-induced arthritis. Arthritis Research & Therapy, 7 Suppl 1: 137-137.


Author Bessis, N .
Bertin-Maghit, S.
Capini, C.
Chomilier, J.
Muller, S.
Zagury, J.F.
Boissier, M.C.
Title Active immunization (vaccination) against peptides of IL-1beta induces self anti-IL-1beta antibodies and protects against collagen-induced arthritis
Formatted title Active immunization (vaccination) against peptides of IL-1β induces self anti-IL-1β antibodies and protects against collagen-induced arthritis
Journal name Arthritis Research & Therapy   Check publisher's open access policy
ISSN 1478-6354
1478-6362
Publication date 2005-02
Sub-type Other
DOI 10.1186/ar1658
Volume 7
Issue Suppl 1
Start page 137
End page 137
Total pages 1
Place of publication London , U. K.
Publisher BioMed Central
Language eng
Subject 1107 Immunology
Formatted abstract 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.
© 2005 BioMed Central Ltd

Keyword Rheumatoid arthritis
Inflammation
Cytokine
Peptides
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Poster

Document type: Journal Article
Sub-type: Other
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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