Effects of pravastatin in murine collagen-induced arthritis.
Here we evaluated whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have beneficial effects for collagen-induced arthritis (CIA). DBA/1 mice were immunized with bovine type-II collagen and administered 100 mg/kg of pravastatin interperitoneally. We measured the effects of pravastatin for CIA including infiltration of macrophages at the synovial membrane and production of anti-type-II collagen antibodies and cytokines. Adverse reactions of pravastatin were also measured. The pravastatin-treated mice had delayed onset of CIA compared with the controls. The involvement of inflammatory cells in the synovial membrane and the expression of monocyte chemotactic protein-1 (MCP-1) mRNA in the joint were reduced. Moreover, some cytokines (TNF-alpha, IL-6, IFN-gamma) and MCP-1 levels in the supernatants of spleen cells cultured with pravastatin decreased. Meanwhile, adverse reactions of pravastatin, such as peritonitis, were not detected. Pravastatin may have good prospects for treating some anti-inflammatory effects on human rheumatoid arthritis.
Yamagata
Toshiaki
T
Department of Nephrology and Rheumatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Kinoshita
Koji
K
Nozaki
Yuji
Y
Sugiyama
Masafumi
M
Ikoma
Shinya
S
Funauchi
Masanori
M
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D024043:Collagen Type II / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D017035:Pravastatin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D024043:Collagen Type II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D003404:Creatinine; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D017035:Pravastatin; D003345:Corticosterone