Background: Cholesterol-lowering drug shows promise against serious infections in sickle cell disease



    Medication already widely used to combat high cholesterol and heart disease might also help protect individuals with sickle cell disease and certain other forms of chronic inflammation from life-threatening bacterial infections.

    Research led by St. Jude Children’s Research Hospital investigators demonstrated the drugs, known as statins, work in several ways to protect some high-risk patients from pneumococcal and possibly other infections. The findings include a newly identified mechanism statins use to keep toxins certain bacteria produce from entering and killing healthy cells.

    The work was done in mice with sickle cell disease. But investigators noted the findings provide a foundation for future research to determine if statins will protect children with sickle cell disease (SCD) from life-threatening pneumococcal infections.

    The pneumococcus is particularly deadly in children with sickle cell, which is an inherited blood disorder affecting the hemoglobin molecule that ferries oxygen throughout the body. The disease is associated with a range of debilitating, sometimes deadly, problems. Young sickle cell patients are 400 times more likely than healthy children or those with other forms of anemia to develop deadly widespread pneumococcal infections.

    In this study, statin-treated mice with sickle cell disease survived longer after pneumococcal infection than untreated SCD mice. There were also indications that statins slowed the spread of the infection from the nasal passage to the lungs and blood streams of SCD mice.

    Researchers found that the statins worked in several ways. Along with disrupting the ability of toxins to enter healthy cells, statins reduced the protein on the cell surface that the bacteria use to infect cells and spread throughout the body. Elaine Tuomanen, M.D., who chairs the St. Jude Department of Infectious Diseases, said the findings suggest statins might also protect against an entire class of bacteria, including diphtheria, tetanus, listeria and group A streptococcus, the so-called flesh-eating bacteria.

    Tuomanen and Carlos Orihuela, Ph.D., of the University of Texas Health Sciences Center at San Antonio, are the study’s senior co-authors.

    The work appears in the January 19 online issue of The Journal of Clinical Investigation. Other authors of this paper include Jason Rosch, the first author; Tamara Pestina, Yunming Hu and Derek Persons (St. Jude) and Angela Boyd and Ernesto Hinojosa (UTHSCSA).

    The work was supported in part by the National Institutes of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, the National Institute on Aging and ALSAC.