Simvastatin treatment modifies polymorphonuclear leukocyte function in high-risk individuals: a longitudinal study.
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.
Guasti
Luigina
L
Department of Clinical Medicine, University of Insubria, Varese, Italy. luigina.guasti@uninsubria.it
Marino
Franca
F
Cosentino
Marco
M
Cimpanelli
Mariagrazia
M
Maio
Ramona C
RC
Klersy
Catherine
C
Crespi
Chiara
C
Restelli
Daniela
D
Simoni
Cinzia
C
Franzetti
Ivano
I
Gaudio
Giovanni
G
Marnini
Patrizio
P
Grandi
Anna M
AM
Lecchini
Sergio
S
Venco
Achille
A
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
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin