Abstract
To assess whether the immunosuppressive effects of atorvastatin outweigh its antibacterial ones in an infection, mice were infected with Escherichia coli and administered atorvastatin; survival rates were then monitored. Mice treated with atorvastatin post-infection showed a remarkable decrease in their survival rate. On the other hand, the higher the level of serum IFN-γ in the infected mice treated with atorvastatin, the lower was the survival rate. Levels of IL-4 were markedly depressed in all groups infected with E. coli and treated with atorvastatin. Since atorvastatin inhibits IFN-γ expression in the absence of bacterial infection, we examined whether bacterial lipopolysaccharide (LPS) was the element capable of overriding this inhibition. Mouse peripheral blood mononuclear cells were treated with atorvastatin and lipopolysaccharide ex vivo then proinflammatory (IFN-γ, TNFα, IL-6) and prohumoral/regulatory (IL-4, IL-13, IL-10) cytokine levels were analyzed in culture supernatants. While proinflammatory cytokine levels were decreased upon treatment with atorvastatin alone, their levels were markedly elevated by treatment with LPS, bacterial lysate or bacterial culture supernatant. On the other hand, atorvastatin exerted an inhibitory effect on production of the prohumoral/regulatory cytokines. Our data indicates that any consideration for statins as antimicrobial treatment should assess the possible adverse outcomes.
Highlights
A myriad of immunomodulatory and anti-inflammatory effects have been attributed to the statins class of antidyslipidemia agents
The survival rate of the group treated with atorvastatin for 4 days pre-infection was 88.9% whereby 1 mouse died on day 6 post-infection; 8 mice remained by the end of the monitoring period
The survival rate of the group infected but not treated with atorvastatin at the end of the monitoring period was 88.9% whereby 1 mouse died on day 2 post-infection; 8 mice remained by the end of the monitoring period
Summary
A myriad of immunomodulatory and anti-inflammatory effects have been attributed to the statins class of antidyslipidemia agents These 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely used in the prevention of cardiovascular disease; numerous non-lipid lowering related effects have been reported for these agents. While some studies and meta-analysis reviews have shown improved infection outcomes, others have shown otherwise; this may be attributed to possible sample size and study biases (reviewed in[13]) To examine this dynamic and assess whether the immunosuppressive effects of statins are more relevant than its antimicrobial effects, we have previously examined an atorvastatin-treated Candida albicans mouse model of infection[14]. In light of the debatable reported improved clinical outcomes of statin treatment in bacterial infections, we examine whether the effects of statins in such an infection differ from those of a fungal one in a mouse model and determine whether particular immune components are affected differently
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