The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial.
OBJECTIVE
To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection.


METHODS
Double-blind placebo controlled randomized clinical trial.


METHODS
Department of medicine and medical intensive care unit in a tertiary university medical center.


METHODS
A total of 83 patients with suspected or documented bacterial infection were enrolled. We randomly assigned 42 patients to receive 40 mg of simvastatin orally, followed by 20 mg of simvastatin, and 41 to receive matching placebo.


RESULTS
The study was prematurely terminated due to slow recruitment rate. Here we report the analysis of the secondary outcome: change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission. Four of the 83 patients enrolled developed severe sepsis, two in each group. No difference was observed in other clinical variables and there were no mortalities. Cytokine levels were randomly assessed in 40 patients (20 in each group). Both TNF-alpha and IL-6 levels were significantly reduced in the simvastatin group (p = 0.02 and p = 0.02, respectively), while no such difference was observed in the placebo group (p = 0.35 and 0.39, respectively).


CONCLUSIONS
Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections. Large controlled trials will determine if this reduction will translate into a clinical benefit.
Novack
Victor
V
Department of Medicine, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University of the Negev, Beersheba, Israel.
Eisinger
Miruna
M
Frenkel
Amit
A
Terblanche
Marius
M
Adhikari
Neill K J
NK
Douvdevani
Amos
A
Amichay
Doron
D
Almog
Yaniv
Y
D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000188:drug therapy*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000517:prevention & control; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D019821:Simvastatin