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IL-23 specific targeting by active immunisation improves inflammation and destruction in a murine model of rheumatoid arthritis
  1. E Assier1,
  2. E Duvallet1,
  3. R Ratsimandresy3,4,
  4. L Delavallee1,
  5. N Bessis1,
  6. J F Zagury3,4,
  7. M C Boissier1,2
  1. 1EA4222, Paris 13 University, Bobigny, France
  2. 2Department of Rheumatology, Avicenne Hospital, APHP, Bobigny, France
  3. 3Chaire de Bioinformatique, CNAM, Paris, France
  4. 4EA3199, CNAM, Paris, France

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Background

Interleukin 23 (IL-23) is a pro-inflammatory cytokine known to be essential for the differentiation of the Th17 lymphocytes, a subtype of T lymphocyte implied in auto-immunity. Its subunit, IL-23 p19, is specific of this cytokine. We had previously demonstrated for IL-1β and tumour necrosis factor α, that active immunisation against these cytokines could be protective in animal models of arthritis.

Objectives

The aim of this study was to evaluate the effect of two vaccines targeting the IL-23 p19 subunit, IL-23-K1 and IL-23-K2, on collagen-induced arthritis (CIA), a model of rheumatoid arthritis.

Methods

Using bioinformatics, we defined two peptides in IL-23 p19. Each peptide was coupled with keyhole limpet haemocyanin (KLH). Anti-murine IL-23 immunisation was performed by injecting intramuscularly IL-23-K1 or IL-23-K2 formulated in incomplete Freund adjuvant (IFA), four times (D0, 7, 28, 49) in DBA/1 mice. Control groups received KLH or phosphate buffered saline (PBS) at the same dates. CIA was induced by t wo subcut aneous injections of bovine t y pe II col lagen, the first at day 40 in complete Freund adjuvant, the second at day 61 in IFA. Anti-IL-23 and anti-K LH antibody levels were assessed by ELISA. Pro-inflammatory and anti-inflammatory cytokines were quantified by qRT-PCR on the spleen and the synovium.

Results

The clinical scores show that mice treated with IL-23-K1 develop less arthritis than the negative controls (p<0.05). Mice vaccinated by IL-23-K1 produced more antiIL-23 antibodies than the one vaccinated by KLH (p<0.001). mRNA quantification showed that the IL-23-K1 vaccination led to an increase of IL-10 in the spleen (p<0.05 vs KLH), without any effect on IL-17 level. Histology examination showed that IL-23-K1 permitted a strong decrease of the joint destruction and inflammation (p<0.01 vs KLH and p<0.001 vs PBS).

Conclusion

These data show that targeting IL-23 p19 using a vaccination strategy may be efficient in CIA.

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Footnotes

  • JFZ and MCB contributed equally to this work

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