Statins Boost Immune System's Ability to Block Pathogenic Bacteria

The statin class of drugs has also been found to increase the ability of the immune system to attack and destroy pathogenic bacteria such as Staphylococcus aureus.

Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent studies have shown a relationship between patients receiving statin therapy and a reduction of mortality associated with severe bacterial infection.

In the current study investigators at the University of California, San Diego (USA) studied the effect of statins on the innate immune capacity of phagocytic cells to destroy the human pathogen S. aureus.

They reported in the November 18, 2010, online edition of the journal Cell Host & Microbe that they had uncovered a beneficial effect of statins on bacterial clearance by phagocytes, although, paradoxically, both phagocytosis and oxidative burst were inhibited. Looking for an extracellular mechanism of killing, they found that statins boosted the production of antibacterial DNA-based neutrophil extracellular traps (NETs) by human and mouse neutrophils and monocytes/macrophages.

Neutrophil extracellular traps (NETs) are networks of extracellular fibers generated by neutrophils that bind pathogens. NETs disarm pathogens with antimicrobial proteins such as neutrophil elastase and histones that are bound to the DNA. NETs provide for a high local concentration of antimicrobial components and bind, disarm, and kill microbes extracellularly independent of phagocytic uptake. In addition to their antimicrobial properties, NETs may serve as a physical barrier that prevents further spread of the pathogens. Furthermore, delivering the granule proteins into NETs may keep potentially injurious proteins like proteases from diffusing away and inducing damage in tissue adjacent to the site of inflammation.

Mice treated with statins were found to be more resistant to staph infections, and phagocytes isolated from these mice were more effective at killing staph bacteria. Treatment in vitro of freshly isolated human white blood cells with statins markedly increased their ability to kill staph bacteria. In each case, the increased killing correlated with greater release of the DNA-based extracellular traps by the phagocytes.

"We found these drugs fundamentally alter how white blood cells behave upon encountering bacteria,” said senior author Dr. Victor Nizet, professor of pediatrics and pharmacy at the University of California, San Diego. "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.”

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University of California, San Diego