Cholesterol-lowering statins boost bacteria-klling cells

Widely prescribed for their cholesterol-lowering properties, recent clinical research indicates that statins can produce a second, significant health benefit: lowering the risk of severe bacterial infections such as pneumonia and sepsis.

A new explanation for these findings has been discovered by researchers at the University of California, San Diego School of Medicine and Skaggs School of Pharmacy & Pharmaceutical Sciences, who describe for the first time how statins activate the bacterial killing properties of white blood cells.

The research is published in the November 18, 2010 issue of Cell Host & Microbe.
Led by Victor Nizet, MD, professor of pediatrics and pharmacy, and Christopher Glass, MD, PhD, professor of medicine and cellular & molecular medicine, the UC San Diego team found that phagocytes (white blood cells that kill and ingest harmful bacteria, foreign particles and dead or dying cells) became more effective after being exposed to statins.

Surprisingly, the statin-induced improvement in bacterial killing did not correspond to increased uptake of bacteria by these specialized white blood cells.  Rather, the researchers found that statins stimulated the phagocytes to release "extracellular traps" – specialized webs of DNA-based filaments embedded with anti-microbial peptides and enzymes capable of ensnaring and killing bacteria before they spread in the body.

A human neutrophil producing DNA-based extracellular traps (stained blue), entrapping the human pathogen bacterium Staphylococcus aureus (green). Three-dimensional structural rendering of Simvastin, a statin.

The findings have broad ramifications, said Glass, given the popularity of statins for controlling high cholesterol levels. Statins are the world's most-prescribed class of medication. An estimated 30 million Americans alone take the drug under commercial names like Lipitor, Zocor and Crestor. ''Clinical research indicates that perhaps 100 million Americans have elevated cholesterol levels that could benefit from statin therapy,'' said Glass. ''Thus any statin-associated changes to immune system function are certain to impact millions of people.''

Prior research had described various anti-inflammatory properties of statins, suggesting that these effects could contribute to a reduction in disease severity during severe infections. Nizet and Glass explored a different hypothesis: That statins might actually aid the body in clearing itself of infectious microbes.  The researchers focused on Staphyloccocus aureus, more commonly called ''staph,'' a frequently antibiotic-resistant human pathogen responsible for everything from minor skin infections to life-threatening meningitis and sepsis.