Background Nitric oxide (NO) regulates the synthesis of several inflammatory mediators, functions of inflammatory cells in the inflamed joint and plays a central role in the regulation of blood vessel tone1. Therefore, NO inhibitors represent important therapeutic advancement in the management of inflammatory diseases. Rosuvastatin improves NO and endothelial dysfunction in patients with heart failure2 but its effect on NO has not yet been tested in Ankylosing Spondylitis (AS) patients.
Objectives To investigate the effect of rosuvastatin on nitrite levels (NO surrogate) and its relationship with endothelial function and inflammatory measures in AS.
Methods 40 consecutive patients (20 in Rosuvastatin (10 mg/day) and 20 in placebo arm) meeting the modified New York criteria for AS, with active disease despite treatment with conventional synthetic DMARDs were recruited. Serum nitrite estimation was carried out by Griess reaction. Flow-mediated dilatation (FMD) was assessed using AngioDefender. Inflammatory measures included– BASDAI, BASFI, ESR and CRP. Pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) were measured at baseline and after 24 weeks.
Results After 24 weeks, significant improvement in serum nitrite was observed in rosuvastatin group (5.27±0.26 to 4.11±0.19, p<0.01) compared with placebo (5.47±0.26 to 5.36±0.23, p=0.33). At 24weeks; FMD, TNF-α, and IL-6 improved significantly in rosuvastatin group compared with placebo. At 24 weeks; ESR, CRP, BASDAI and BASFI significantly improved in rosuvastatin group compared with placebo. After treatment with rosuvastatin, nitrite correlated inversely with FMD (r=-0.47, p=0.03) (Fig.1A) and positively with TNF-α (r=0.64, p=0.01) (Fig.1B), CRP (r=0.52, p=0.01) (Fig.1C) and LDL (r=0.54, p=0.01) (Fig.1D).
Conclusions Rosuvastatin reduced serum nitrite concentration and improved endothelial dysfunction in AS patients. Rosuvastatin lowers the proinflammatory cytokines, especially IL-6 and TNF-α, which downregulates CRP production and thus the production of NO. Rosuvastatin also favorably improved the lipid levels in AS patients. Rosuvastatin exerts anti-inflammatory, immunomodulatory and vasculoprotective effect in ankylosing spondylitis through both cholesterol dependent and cholesterol independent pathways
Sharma et al. Inflammopharmacology 2007;15:252–9.
Schäfer et al. Arterioscler Thromb Vasc Biol 2005;25:1071–1077.
Disclosure of Interest None declared
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