St. Jude Children's Research Hospital scientists lead effort that identifies a novel way statins protect cells from a host of bacterial toxins
New research suggests a family of widely used cholesterol-lowering drugs might help protect individuals from serious illness following bacterial infection, including the pneumococcal infections that pose a deadly threat to those with sickle cell disease.
Research led by St. Jude Children's Research Hospital investigators reported that drugs called statins employ several methods to dampen inflammation and block pneumococcus and certain other bacteria from infecting cells and spreading throughout the body. Elaine Tuomanen, M.D., St. Jude Infectious Diseases chair, said those methods include a newly identified mechanism that statins use to protect healthy cells by blocking the toxicity of an entire class of bacteria. Along with pneumococcus, that class includes diphtheria, tetanus, listeria and group A streptococcus, which is also known as the flesh-eating bacterium.
Tuomanen is co-senior author of the study with Carlos Orihuela, Ph.D., University of Texas Health Science Center at San Antonio (UTHSCSA). The work is published in the January 19 advanced, online edition of The Journal of Clinical Investigation.
The results provide the foundation for a possible future study to determine if statins, already widely used to lower cholesterol in adults, might protect children with sickle cell disease (SCD) from serious pneumococcal infection. SCD is an inherited blood disorder. The findings also suggest statins might protect others at high risk for pneumonia due to chronic inflammation of the lungs or blood vessels.
In this study, scientists reported that statins prolonged the lives of mice with sickle cell disease following infection with the pneumococcal bacteria. Researchers also reported that a day after being infected, the treated mice had fewer bacteria in their lungs and blood, suggesting statins slowed the spread of the infection.
Tuomanen said statins did not cure the mice, but prolonged their survival. She said the extra time might make a life-or-death difference in humans by keeping patients alive long enough for other medications to kill the bacteria.
The research reflects the long-standing interest of St. Jude investigators in both sickle cell and pneumococcal and other infectious diseases. Tuomanen said it is also an example of the insights gained when basic and clinical investigators collaborate.
Pneumococcal infection is the leading cause of lethal pneumonia in children worldwide. The bacterium poses an even greater threat to children with SCD. They are 400 times more likely than their healthy counterparts to develop widespread, potentially fatal pneumococcal infections.
Sickle cell is the most common genetic disorder worldwide. In the U.S., the disease most often strikes those of African ancestry. About one in every 375 African American newborns inherits the mistake in instructions for assembling the hemoglobin protein, which is responsible for ferrying oxygen throughout the body. As a result, their red blood cells sometimes change from a pliable, disc shape to a brittle, sickled shape. The sickled cells are unable to move easily through tiny blood vessels, disrupting circulation and leaving affected individuals at risk for a variety of debilitating and deadly problems, including infections.
The risk posed by the pneumococcus is so great that young sickle cell patients are prescribed a daily dose of penicillin in hopes of preventing the infection. Investigators 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.