HSP 90 inhibitors, which are finding favor in fighting cancer, may also help battle overwhelming infection in intensive care patients, researchers say.
Studies in an animal model of sepsis, a major cause of ICU patient death, indicate HSP 90 inhibitors help degrade proteins perpetuating inflammation, says Dr. John D. Catravas, director of the Medical College of Georgia Vascular Biology Center.
Results include restored lung function, reduced blood vessel leakage, which can lead to dangerous swelling in the lungs, and fewer byproducts of inflammation such as white blood cells, MCG researchers report in the American Journal of Respiratory and Critical Care Medicine, a journal of the American Thoracic Society.
They already have begun looking at the impact of HSP 90 inhibitors on the function of other organs, such as the liver and kidneys, also typically impacted by sepsis.
“We would die without an inflammatory response, but unreined inflammation is bad,” says Dr. Catravas. That's just what happens with overwhelming infection; inflammation, which helps the body eliminate invaders, essentially keeps working after invaders are gone and the new target is the body.
“These are proteins that initially are useful in combating an invading bacteria but then, in some of us that develop sepsis for reasons that are poorly understood, the inflammatory response is amplified and stays much longer than it should,” says Dr. Catravas, the paper's corresponding author.
Heat shock proteins carry proteins where they are needed and fold them up nicely so they do the correct job. Dr. Catravas compares their two-protein configuration to a lobster with its claws closed while tending to “client” proteins.
“The hypothesis we worked on is that these HSP 90 inhibitors take the heat shock protein and move it into a different conformation,” says Dr. Catravas. The published research indicates they were correct and that inhibitors, fortunately, readily target proteins that no longer have a useful function.