d-4f-peptide and Arthritis--Rheumatoid

To evaluate the therapeutic potential of an apolipoprotein A-1 (apoA-1) mimetic peptide, D-4F, in combination with pravastatin in collagen-induced arthritis (CIA), syngeneic Louvain rats were immunized with type II collagen and randomized to vehicle control, D-4F monotherapy, pravastatin monotherapy, or D-4F + pravastatin combination therapy. Clinical arthritis activity was evaluated and radiographs, type II collagen antibody titers, cytokine/chemokine levels, and HDL function analysis were obtained. There was significant reduction in clinical severity scores in the high and medium dose D-4F + pravastatin groups compared to controls (p< or =0.0001). Reduction in erosive disease occurred in the medium/high dose combination groups compared to non-combination groups (p< or =0.01). Favorable changes in cytokines/chemokines were noted with treatment, and response to combination D-4F/pravastatin therapy was associated with improvement in HDL's anti-inflammatory properties. Combination D-4F/pravastatin significantly reduced clinical disease activity in CIA, and may have dual therapeutic potential in other autoimmune diseases with increased cardiovascular morbidity and mortality.

Topics: Animals; Antibodies; Anticholesteremic Agents; Apolipoprotein A-I; Arthritis, Experimental; Arthritis, Rheumatoid; Chemotaxis; Cholesterol, HDL; Collagen Type II; Cytokines; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Histocytochemistry; Humans; Joints; Monocytes; Pravastatin; Radiography; Random Allocation; Rats; Regression Analysis