title: Simvastatin treatment modifies polymorphonuclear leukocyte function in high-risk individuals: a longitudinal study.
abstract: BACKGROUND
  Although extensive experimental evidence supports a primary role of polymorphonuclear leukocytes (PMNs) in atherosclerosis, few data exist concerning the functional properties of these cells and their pharmacological modulation in high-risk individuals.
  
  
  OBJECTIVE
  The production of the proinflammatory chemokine interleukin-8 (IL-8), migration and chemotaxis, and reactive oxygen species (ROS) generation were investigated in a longitudinal study in PMNs obtained from high-risk individuals during statin treatment. As a secondary endpoint we compared PMN function of high-risk patients with that of controls.
  
  
  RESULTS
  PMNs were isolated from 21 high-risk individuals before treatment and 3 and 30 days after the beginning of simvastatin treatment, and from healthy controls. During treatment a significant reduction was observed both in resting (P = 0.009) and N-formyl-Met-Leu-Phe (fMLP)-stimulated (P = 0.008) IL-8 production, and in the chemotactic index (P = 0.038), whereas ROS generation did not significantly change. In comparison with cells from controls, PMNs obtained from patients before starting simvastatin treatment showed higher resting and fMLP-stimulated IL-8 release (P = 0.007 and P = 0.002, respectively) and ROS generation (resting, P = 0.009; and fMLP-stimulated, P = 0.046), whereas migration and the chemotactic index did not significantly differ.
  
  
  CONCLUSIONS
  An activation of neutrophils is present in high-risk individuals, shown by the enhanced production of IL-8, and increased ROS generation. The 4-week statin treatment is able to reduce the cell capability to produce IL-8, and to decrease chemotaxis, thus affecting the proinflammatory properties of PMNs.
authors.affiliation: Department of Clinical Medicine, University of Insubria, Varese, Italy. luigina.guasti@uninsubria.it
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Cimpanelli
authors.forename: Ramona C
authors.initials: RC
authors.lastname: Maio
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Chiara
authors.initials: C
authors.lastname: Crespi
authors.forename: Daniela
authors.initials: D
authors.lastname: Restelli
authors.forename: Cinzia
authors.initials: C
authors.lastname: Simoni
authors.forename: Ivano
authors.initials: I
authors.lastname: Franzetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudio
authors.forename: Patrizio
authors.initials: P
authors.lastname: Marnini
authors.forename: Anna M
authors.initials: AM
authors.lastname: Grandi
authors.forename: Sergio
authors.initials: S
authors.lastname: Lecchini
authors.forename: Achille
authors.initials: A
authors.lastname: Venco
mesh_terms: D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D012307:Risk Factors; D019821:Simvastatin / Q000494:pharmacology*; D014652:Vascular Diseases / Q000517:prevention & control
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin