Simvastatin reduces leucocyte- and platelet-endothelial cell interaction in murine antigen-induced arthritis in vivo.
OBJECTIVE
The use of statins in the prevention and treatment of cardiovascular diseases is well established. Their use as anti-inflammatory and immunomodulatory agents in the treatment of rheumatoid arthritis (RA) has also been investigated, with several clinical and experimental studies indicating an anti-inflammatory effect of statins for RA, but other studies showing no effect or even the opposite. The current study was designed to examine the effect of simvastatin in an in vivo murine model of arthritis using intravital microscopy.


METHODS
We assigned four groups (n = 7, female C57Bl6 mice), two with and two without antigen-induced arthritis (AiA), from which one of the non-AiA groups and one of the AiA groups were treated with simvastatin 40 mg/kg i.p. daily for 14 consecutive days after induction of arthritis. Platelet- and leucocyte-endothelial cell interaction was assessed by measurement of rolling and adherent fluorescence-labelled platelets and leucocytes, functional capillary density (FCD) was evaluated, and knee joint diameter was determined as a clinical parameter.


RESULTS
In arthritic mice treated with simvastatin, a significant reduction in platelet- and leucocyte-endothelial cell interaction was observed in comparison to arthritic mice treated with vehicle. In addition, a significant reduction in FCD was seen in arthritic mice treated with simvastatin, along with a reduction in knee joint swelling of the AiA mice.


CONCLUSIONS
Treatment of AiA mice with simvastatin showed significant reductions in platelet- and leucocyte-endothelial cell interactions, in FCD, and in the swelling of the knee joint. These results support the hypothesis of the anti-inflammatory effects of statins in the treatment of RA.
Walter Brendel Centre, Ludwig Maximilians University of Munich , Bernau-Felden , Germany.
O
O
Gottschalk
M L
ML
Dao Trong
P
P
Metz
J
J
Wallmichrath
S
S
Piltz
K W
KW
Jauch
V
V
Jansson
M
M
Schmitt-Sody
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000941:Antigens / Q000009:adverse effects*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D019821:Simvastatin / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000941:Antigens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin