title: Inhibition of adjuvant-induced arthritis by nasal administration of novel synthetic peptides from heat shock protein 65.
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.
authors: Xiao-Lian
authors: XL
authors: Shi
authors: Li-Ping
authors: LP
authors: Wang
authors: Xuan
authors: X
authors: Feng
authors: Dan-Dan
authors: DD
authors: Fan
authors: Wei-Jin
authors: WJ
authors: Zang
authors: Bing
authors: B
authors: Wang
authors: Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P,R, China. jzhou829@126.com.
authors: Jun
authors: J
authors: Zhou
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000138:chemical synthesis; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D001426:Bacterial Proteins / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D018834:Chaperonin 60 / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000138:chemical synthesis; D011917:Rats, Inbred Lew; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D001426:Bacterial Proteins; D015415:Biomarkers; D018834:Chaperonin 60; D018836:Inflammation Mediators; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C074119:heat-shock protein 65, Mycobacterium; D015847:Interleukin-4