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Cholesterol-Lowering Drug Shows Promise Against Serious Infections in Sickle Cell Disease
Date:1/19/2010

gators noted that emergence of pneumococcal bacteria resistant to penicillin underscores the need for new prevention tools.

Statins interfere with the liver's ability to make cholesterol. Several years ago researchers noted possible links between statins and a reduced risk of respiratory infections and sepsis.

In this study, researchers showed statins work in part by dampening expression of the protein found on the surface of cells that pneumococcus uses to gain entry into the cells. That protein is called the platelet-activating factor receptor or PAFr. A variety of factors influence how much PAFr is found on the surface of cells. The chronic inflammation associated with sickle cell and certain other diseases leads to increased PAFr production by cells lining the blood vessels and in the lungs.

Investigators used several methods to show statins reduced the number of PAF receptors on the surface of cells both in the laboratory and in the lungs of mice with SCD. In the laboratory, the suppression of the receptor was reversible with the addition of a compound that blocked statin activity.

But Jason Rosch, Ph.D., said PAFr turned out to be just part of the story. Rosch is a St. Jude postdoctoral fellow and the paper's lead author.

Investigators reported statins even helped sickle cell mice that lacked the genetic instructions for making the mouse version of PAFr battle pneumococcal infection more effectively. The statin-treated mice lived longer and had fewer bacteria in their blood. The drug had no impact on mice that lacked PAFr, but did not have sickle cell disease. Rosch said that suggested statins work in part by reducing inflammation associated with sickle cell disease.

Researchers also found statins interfere with the mechanism by which poisons, or toxins, pneumococcus and other bacteria produce are taken up into cells. Those toxins rely on cholestero
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SOURCE St. Jude Children's Research Hospital
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