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Simvastatin inhibits neutrophil degranulation induced by anti-neutrophil cytoplasm auto-antibodies and N-formyl-methionine-leucine-phenylalanine (fMLP) peptide

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Author(s): Bahjat Al-Ani

Journal: Saudi Medical Journal
ISSN 0379-5284

Volume: 34;
Issue: 5;
Start page: 477;
Date: 2013;
Original page

ABSTRACT
Objectives: To test the hypothesis that simvastatin is capable of blocking human neutrophil degranulation induced by proteinase 3 (PR3)-anti-neutrophil cytoplasm auto-antibodies (ANCA) and myeloperoxidase (MPO)-ANCA, and by the chemotactic and inflammatory peptide N-formyl-methionine-leucine-phenylalanine (fMLP). Methods: This study was conducted between March 2010 and September 2011 at the Renal Institute of Birmingham, University of Birmingham, Birmingham, United Kingdom. Immunoglobulin G (IgG) was purified from the plasma of 20 randomly selected patients with ANCA-associated vasculitis (10 PR3- and 10 MPO-ANCA), and their ability to induce neutrophil degranulation in the presence or absence of simvastatin (10 μM) was tested. The ability of the same dose of simvastatin to block fMLP-induced neutrophil degranulation was also tested. In addition, the ability of serum obtained from rats that received simvastatin at a dose of 25 mg/kg/day to block neutrophil degranulation in vitro was tested. Results: The addition of simvastatin significantly inhibited ANCA IgG-induced neutrophil degranulation by 48% (p=0.02). There was no significant difference in response to simvastatin inhibition (p=0.73) between PR3- and MPO-ANCA. Simvastatin also inhibited neutrophil degranulation induced by 1 μM fMLP (30%, p=0.04). We further demonstrated that serum from rats that received simvastatin significantly inhibited neutrophil degranulation induced by ANCA (31.7%, p=0.01) and fMLP (23.5%, p=0.03) compared to serum from control animals.   Conclusion: Simvastatin blocked both ANCA and fMLP-induced neutrophil degranulation. It is worth pursuing further therapeutic investigation of statins in vascular inflammatory diseases that involve neutrophil degranulation in their pathogenesis. 
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