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

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 what they claim is the first time—exactly how statins activate the bacterial-killing properties of white blood cells. The research was published last month in an issue of the medical journal Cell Host & Microbe.

Led by Drs. Victor Nizet and Christopher Glass, 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. Nizet is a professor of pediatrics and pharmacy at the university, and Glass is a professor of cellular and molecular medicine.

Surprisingly, the statin-induced improvement in killing bacteria didn't correspond to increased uptake of bacteria by these specialized white blood cells, the researchers say. Rather, they say they 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.

The findings have broad ramifications, says Glass, given the popularity of statins for controlling high cholesterol levels. Statins are the world's most-prescribed medication. About 30 million Americans alone take the drugs 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," says 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 some infections. Nizet and Glass explored a different hypothesis—that statins actually might 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.

Mice treated with statins were more resistant to staph infections than other mice, and phagocytes isolated from these mice were more effective at killing staph bacteria. Simple exposure of freshly isolated human white blood cells to statins in a test tube markedly increased their ability to kill staph and other important disease-causing bacteria. In each case, the increased killing correlated with greater release of the DNA-based extracellular traps by the phagocytes.

The UC San Diego findings demonstrate that statins have important pharmacological effects beyond inhibiting cholesterol production, researchers say.

"We found these drugs fundamentally alter how white blood cells behave upon encountering bacteria," Nizet says. "In our studies with staph bacteria, the net effect of statin treatment was to improve bacterial killing and extracellular trap formation. These same changes might not be so consequential for defense against less virulent bacteria that are easily susceptible to uptake and killing within phagocytes."

The research also sheds new light on the clinical phenomenon of reduced infection severity in patients receiving statins, the scientists say. It indicates that levels of cholesterol or related lipid molecules can be sensed by white blood cells and used as signals to control inflammatory and antibacterial activities. Nizet and Glass recommend that research explore whether the potential of cholesterol-lowering agents combined with antibiotics can be harnessed to optimize the treatment of certain difficult infectious disease conditions.