Researchers have discovered how a specific protein regulates the inflammatory response in sudden lung failure, reports the August issue of Nature Medicine.
Acute Respiratory Distress Syndrome (ARDS) is a complication of severe traumatic injury, bacterial infections, blood transfusions, and overdoses of some medications in which the lungs become swollen with fluid causing total respiratory impairment. With a 30% to 40% rate of fatality, the condition has no effective treatment.
"Without an inflammatory response, bacterial invaders in the lungs can kill, but too intense a response can also be fatal," said Kurt Bachmaier, MD, PhD, research assistant professor in pharmacology at University of Illinois at Chicago Medical College and first author of the study.
After creating a mouse model that lacked the gene for Cblb protein, which triggers an auto-immune response through the regulation of T- and B-cells, the mice were much less likely to survive because the receptor for inflammatory cytokines and chemokines stays on the surface of lung tissue cells, thereby lethally prolonging the inflammatory response.
The researchers also showed that a protein that controls the production of inflammatory cytokines, called NF-kB, is induced in lung tissue after sepsis by that receptor to a much greater extent in the Cblb-deficient mice than in normal mice. NF-kB is known to induce swelling of tissues.
"There are already early-stage drug trials of treatments for ARDS targeting NF-kB," said Bachmaier. "This discovery has real clinical implications in the treatment and prevention of life-threatening lung failure."
Cblb is a potential drug target that may lead to a new class of anti-bacterial drugs, says Asrar Malik, MD, PhD, head of pharmacology at UIC and a senior author on the paper. Malik and Bachmaier have recently filed a patent on the basis of these findings.