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Open Access Research article

Inhibition of adjuvant-induced arthritis by nasal administration of novel synthetic peptides from heat shock protein 65

Xiao-Lian Shi1, Li-Ping Wang1, Xuan Feng1, Dan-Dan Fan1, Wei-Jin Zang1, Bing Wang2 and Jun Zhou1*

Author Affiliations

1 Department of Pharmacology, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061, P.R. China

2 Department of Pathology and Therapeutic Vaccines Engineering Center, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061, P.R. China

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BMC Musculoskeletal Disorders 2014, 15:253  doi:10.1186/1471-2474-15-253

Published: 25 July 2014

Abstract

Background

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease mediated by T cells. The aim of the present study was to investigate the therapeutic efficacy of synthetic peptides (HP-R1, HP-R2 and HP-R3), derived from the sequence of 65-kD mycobacterial heat shock protein (HSP), in the treatment of RA using adjuvant-induced arthritis (AA) animal model.

Methods

AA was induced by a single intradermal injection Freund’s complete adjuvant in male Lewis rats. At the first clinical sign of disease, rats were administered nasally by micropipette of peptides or phosphate buffer saline (PBS). Disease progression was monitored by measurement of body weight, arthritis score and paw swelling. The changes of histopathology were assessed by hematoxylin eosin staining. The serum levels of tumor necrosis factor (TNF) - alpha and interleukin (IL)-4 were measured by enzyme-linked immunosorbent assay (ELISA).

Results

The peptides efficiently inhibited the footpad swelling and arthritic symptoms in AA rats. The synthetic peptides displayed significantly less inflammatory cellular infiltration and synovium hyperplasia than model controls. This effect was associated with a suppression of pro-inflammatory cytokine TNF-alpha production and an increase of anti-inflammatory cytokine IL-4 production after peptides treatment.

Conclusions

These results suggest that the synthetic peptides derived from HSP65 induce highly effective protection against AA, which is mediated in part by down-regulation of inflammatory cytokines, and support the view that the synthetic peptides is a potential therapy for RA that may help to diminish both joint inflammation and destruction.

Keywords:
Adjuvant arthritis; Synthetic peptides; Inflammatory cytokines; Heat shock protein