title: Simvastatin inhibits neutrophil degranulation induced by anti-neutrophil cytoplasm auto-antibodies and N-formyl-methionine-leucine-phenylalanine (fMLP) peptide.
abstract: OBJECTIVE
  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 uM) 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 uM 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia. bahjat_alani@yahoo.com
authors.forename: Bahjat
authors.initials: B
authors.lastname: Al-Ani
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D011921:Rats, Inbred WKY; D019821:Simvastatin / Q000494:pharmacology*; D014657:Vasculitis / Q000097:blood / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019821:Simvastatin