Anti-Arthritic Effects of Immunomodulatory Peptide Injected in Joints

Yun      Lu; Raghwa      Sharma; Marina      Ali; Karen      Byth; Nicholas      Manolios

Abstract

Objective: To examine the clinical and histological outcomes following intra-articular injection of an immunomodulatory peptide (CP) during an acute attack of adjuvant induced arthritis in rats. Methods: Arthritis in rats was induced by injecting 0.1mL of Mycobacterium Tuberculosis (MTB; 10mg/ml) intra-dermally at the base of the tail. After the onset of arthritis, affected ankle joints were injected with either 20μl of water, dexamethasone (4mg/ml), cyclosporine (0.38mg; equivalent to 3mg/kg in humans), CP (60mg/ml; 12.5 mg/ml; 6.25 mg/ml; 3.125 mg/ml) or a CP analogue (CPD; 6.25mg/ml). There were a minimum of 5 rats/group and intra-articular injection was given on two separate occasions following the onset of arthritis. Rat weight, paw thickness, paw-width, ankle width and arthritic joint count were measured. Affected joints were X-rayed and joint tissue taken for histology. Results: Rats given dexamethasone and cyclosporine had a significant improvement in clinical outcomes compared to the control group. CP at the highest dose was significantly better compared to the water group and the clinical effects were dose dependent. Histology of the joints showed severe inflammation and destruction in the water treated group with minimal inflammatory effects in the dexamethasone and cyclosporine group. Joints injected with cyclosporine were characterized by extensive fibrosis. The joints from CP treated rats showed mild to moderate inflammation with histological features somewhere between the cyclosporine and water injected groups. Conclusion: This study demonstrates that CP given intra-articularly has antiarthritic effects and raises new possibilities for treatment.

Keywords: Inflammation, animal model, adjuvant induced arthritis, peptides, therapeutics, intra-articular injection, Arthritis, core peptide, drug delivery