Study Uncovers the Mechanisms behind Inflammation in Healing Pneumonia
In a new study done on animals, researchers from the University of Pittsburgh School of Medicine uncovered new mechanisms that the immune system uses in order to increase inflammation and fight pneumonia. The scientists found a new biological pathway that shows how the body fights pneumonia, and how that process can become negative since some cases of pneumonia have led to excessive inflammation. The pathway allows researchers to witness how the immune system innately improves the chances for survival and lung function and how certain agents might be blocking that response.
"In our ongoing studies of pneumonia, we found infecting bacteria activate a previously unknown protein called Fbxo3 to form a complex that degrades another protein called Fbxl2, which is needed to suppress the inflammatory response," said Dr. Rama Mallampalli, who is a professor and vice chair for research at the Department of medicine. He is also the director of the Acute Lung Injury Center of Excellence as the University and the chief of the pulmonary division of the VA Pittsburgh Healthcare System. "The result is an exaggerated inflammatory response that can lead to further damage of the lung tissue, multi-organ failure and shock."
The researchers explained that infections like pneumonia could cause the body to react with excessive inflammation, which is considered to be detrimental for the body. The research team, led by Bill B Chen, Ph.D., who is an associate professor of the Division of Pulmonary, Allergy and Critical Care Medicine, looked at 16 blood samples from people who suffered from a condition of systemic inflammation known as sepsis. The team discovered that these people had higher levels of Fbxo3 in comparison to the seven blood samples from people who did not have sepsis. In order to understand why and how inflammation becomes harmful, the researchers looked into the protein Fbxo3.
They concluded that the presence of Fbxo3 appears to hinder the bodies' natural response to fight off the infection, which leads to prolonged inflammation. The researchers experimented on mice that did not have Fbx03 by injecting them with a strain of Pseudomonas bacteria and observing how their bodies attacked the infection. They found that these mice were able to survive longer and had better lung function when compared to mice with the protein.
"The key is to find ways to help the body temper its inflammatory response so that it's able to kill the infectious agent without causing injury to healthy tissue," Dr. Mallampalli said.
Based from the findings, the research team developed a group of small molecules aimed to prevent Fbxo3 from being activated. One of the molecules, called BC-1215 has shown success in reducing inflammatory markers and improving lung functions within the lab setting. The research team is now looking into how BC-1215 can be used in other cases of systemic inflammation.
The findings were published in Nature Immunology.