Complement activation plays a relevant role in the development of tissue damage under inflammatory conditions, and clinical and experimental observations emphasize its contribution to inflammatory
vasculitides.
Statins have recently been shown to reduce cardiovascular morbidity independently of plasma
cholesterol lowering and in vitro studies support a direct anti-inflammatory action of these drugs. The aim of this study was to verify the in vivo effect of
fluvastatin on
complement-mediated acute peritoneal
inflammation. The effect of oral treatment with
fluvastatin was investigated in normo-cholesterolaemic rats that received
intraperitoneal injection of either yeast-activated rat serum (Y-act RS) or
lipopolysaccharide to induce peritoneal
inflammation monitored by the number of PMN recruited in peritoneal fluid washes. In addition, vascular adherence and extravasation of leucocytes were evaluated by direct videomicroscopy examination on mesentery postcapillary venules topically exposed to Y-act RS. The number of PMN in the peritoneal washes of rats treated with
fluvastatin was 38% lower than that of untreated animals (P < 0.05) 12 h after LPS injection, and was even lower (56%) in rats treated with Y-act RS already 8 h after injection (P < 0.02). Firm adhesion to endothelium and extravasation of leucocytes evaluated under direct videomicroscopy observation were significantly inhibited in
fluvastatin treated rats (77% and 72%, respectively; P < 0.01), 120 min
after treatment with Y-act RS. Our results demonstrate that
fluvastatin inhibits in vivo
complement-dependent acute peritoneal
inflammation and suggest a role for
statins in preventing the inflammatory flares usually associated with complement activation in
chronic diseases, such as SLE or
rheumatoid arthritis.