Treatment with an apolipoprotein A-1 mimetic peptide in combination with pravastatin inhibits collagen-induced arthritis.
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.
Charles-Schoeman
Christina
C
Division of Rheumatology, at the UCLA David Geffen School of Medicine, 1000 Veteran Avenue, Room 32-59, Los Angeles, CA, USA. ccharles@mednet.ucla.edu
Banquerigo
Mona Lisa
ML
Hama
Susan
S
Navab
Mohamad
M
Park
Grace S
GS
Van Lenten
Brian J
BJ
Wagner
Alan C
AC
Fogelman
Alan M
AM
Brahn
Ernest
E
D000818:Animals; D000906:Antibodies / Q000097:blood; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D002633:Chemotaxis; D008076:Cholesterol, HDL / Q000097:blood; D024043:Collagen Type II / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006651:Histocytochemistry; D006801:Humans; D007596:Joints / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D017035:Pravastatin / Q000494:pharmacology*; D011859:Radiography; D011897:Random Allocation; D051381:Rats; D012044:Regression Analysis
D000906:Antibodies; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D024043:Collagen Type II; D016207:Cytokines; C465468:D-4F peptide; D017035:Pravastatin