title: Fluvastatin and lovastatin inhibit granulocyte macrophage-colony stimulating factor-stimulated human eosinophil adhesion to inter-cellular adhesion molecule-1 under flow conditions.
abstract: BACKGROUND
  Eosinophil accumulation in the lung is an important feature of airway inflammation in asthma. There is therefore much interest in developing novel therapies to prevent this process. Accumulating evidence suggests that statins have anti-inflammatory properties, including inhibition of leucocyte accumulation. We therefore assessed the ability of five statins to inhibit human eosinophil adhesion to recombinant human inter-cellular adhesion molecule (rhICAM)-1 under physiologically relevant flow conditions.
  
  
  METHODS
  Purified eosinophils were pre-treated with a panel of statins before elucidation of the adhesion profiles of resting and granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells to rhICAM-1-coated microchannels at a flow rate of 0.5 dynes/cm(2). Images were recorded in real-time at 1 min intervals and analysed using Ducocell software.
  
  
  RESULTS
  Fluvastatin and lovastatin (both 10 nm) significantly inhibited GM-CSF-stimulated eosinophil adhesion to rhICAM-1 after 2 min (34.4+/-3.0% inhibition and 37.8+/-12.6% inhibition, respectively, n=4, P<0.05) but had no significant inhibitory effect on unstimulated eosinophil adhesion. Mevastatin, simvastatin, and pravastatin (all 10 nm) had no significant effect on GM-CSF-stimulated eosinophil adhesion to rhICAM-1. A concentration range of fluvastatin and lovastatin inhibited GM-CSF stimulated eosinophil adhesion with significant (P<0.05) inhibition observed at low concentrations of 1 nm for both drugs. Mevalonate (100 nm) reversed fluvastatin-mediated but not lovastatin-mediated inhibition of eosinophil adhesion.
  
  
  CONCLUSIONS
  Inhibition of eosinophil adhesion to ICAM-1 by fluvastatin and lovastatin under physiological shear stress represent novel actions by these drugs that may inform the development of anti-inflammatory therapy for allergic disease.
authors.affiliation: Section of Immunology & Infection, Division of Applied Medicine, School of Medicine & Dentistry, University of Aberdeen, Aberdeen, Scotland, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Robinson
authors.forename: D
authors.initials: D
authors.lastname: Kashanin
authors.forename: F
authors.initials: F
authors.lastname: O'Dowd
authors.forename: K
authors.initials: K
authors.lastname: Fitzgerald
authors.forename: V
authors.initials: V
authors.lastname: Williams
authors.forename: G M
authors.initials: GM
authors.lastname: Walsh
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000378:metabolism; D008798:Mevalonic Acid / Q000494:pharmacology; D046210:Microfluidic Analytical Techniques; D044085:Microfluidics; D017035:Pravastatin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C012258:mevastatin; D000077340:Fluvastatin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin; D008798:Mevalonic Acid