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The mode of anti-arthritic peptide delivery impacts on the severity and outcome of adjuvant induced arthritis

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Abstract:

Abstract Aim: 

A synthetic nonapeptide (core peptide [CP]) was tested as a potential therapeutic agent for the treatment of acute onset arthritis. Differing modes of delivery (subcutaneous [SCI]vs. intraperitoneal [IP]) and lipid conjugation of CP were examined. Methods: 

Wistar rats aged 9–12 weeks were injected SCI in the tail with 1 mg of heat-killed Mycobacterium tuberculosis (MTB) to bring about adjuvant induced arthritis. After development of arthritis (day 12), 6 mg of CP, 6 mg of CP-lipid conjugate (LP), or 1.2 mg cyclosporin A (Csp; 3 mg/kg) in 100 µL of diluent were given SCI or IP for 4 consecutive days. Severity of arthritis was assessed by changes in body weight, paw thickness, paw and ankle width, and the total number of arthritic joints involved up to 7 days after the first onset of arthritis and the commencement of treatment. Results: 

Core peptide and LP given either SCI or IP were effective in the treatment of acute adjuvant induced arthritis. IP administration of LP was significantly better than that of control and CP-treated rats (P < 0.05) when examined at two separate time points, day 4 and day 7, after commencement of treatment. The effectiveness of IP-administered LP was comparable to cyclosporin. Conclusions: 

CP-lipid conjugate and CP have a therapeutic benefit in the treatment of acute arthritis. The mode of delivery and lipid conjugation of CP influences the efficacy and outcome of arthritis.

Keywords: T lymphocytes; animal disease models; immunosuppression; peptides; therapeutics

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1479-8077.2007.00289.x

Affiliations: 1: Department of Rheumatology, and 2: Westmead Millenium Institute, Westmead Hospital, Sydney, New South Wales, Australia

Publication date: September 1, 2007

bsc/apl/2007/00000010/00000003/art00006
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