- Paper Report
- Open Access
Nasal administration of an altered peptide of Hsp60 can treat adjuvant arthritis
- Lucy Wedderburn1
© Biomed Central Ltd 2002
- Received: 5 September 2002
- Accepted: 19 September 2002
- Published: 19 September 2002
- animal model
- nasal tolerance
- regulatory T cell.
There is continued interest in mechanisms of tolerance induction in inflammatory arthritis. The induction of tolerance to peptides derived from heat shock proteins (Hsp), by oral or nasal administration, has been shown to be a method of partially suppressing arthritis in the rat adjuvant induced arthritis (AIA) model. In this study the authors used an altered peptide of the Hsp 60 molecule, 180-188183L-Ain which amino acid 183 has been mutated from leucine to alanine, to induce tolerance and to suppress arthritis. This peptide has a higher binding affinity for the rat class II major histocompatibility complex (MHC) molecule (RT1.B1) than the parent hsp180-188 peptide.
Administration of 180-188183L-A led to a profound reduction in incidence and severity of disease compared to controls, and could also reduce disease when given to animals who already had established arthritis. This protection could be transferred to naïve animals using concanavalin (Con-A) activated splenocytes from animals given 180-188183L-A. Mandibular lymph node cells specific for 180-188183L-A after nasal tolerance induction produced interleukin (IL)-10 as well as IL-4 and transforming growth factor (TGF)β. The use of anti-IL-10 antibody could block suppression in vitro while anti-IL-4 and anti-TGFβ did not alter the suppressive effect of lymph node cells on proliferation to hsp60.
Adoptive transfer, animal model adjuvant induced arthritis, cytokine staining, ELISA, proliferation assay.
- Prakken BJ, Roord S, van Kooten PJ, Wagenaar JP, van Eden W, Albani S, Wauben MH: Inhibition of adjuvant-induced arthritis by interleukin-10-driven regulatory cells induced via nasal administration of a peptide analog of an arthritis-related heat-shock protein 60 T cell epitope. Arthritis Rheum. 2002, 46(7): 1937-1946.View ArticleGoogle Scholar