There is emerging evidence that suggests the importance of the liver in sepsis patients who are at risk of developing subsequent pneumonia. This is the first report directly demonstrating a link between a key mediator produced by the liver and how the body responds to an infection.
Led by researchers Boston University School of Medicine (BUSM), the study appears in the journal Infection and Immunity, which is published by the American Society for Microbiology.
Sepsis is a complex syndrome characterized by systemic inflammatory response and is a frequent problem encountered in intensive care units. Depending on severity, sepsis can lead to organ dysfunction or failure and even death with mortality rates estimated to be 30 to 50 percent. Crucially, sepsis can actually suppress the immune system leaving patients to be vulnerable to secondary infections, especially pneumonia.
One of the common themes between sepsis and infection is the regulation of the inflammatory response by the immune system. The liver plays a crucial role in modulating the immune system by inducing the hepatic acute phase response which, among other things, helps fight the infection. A key factor is STAT3, which has been shown to activate the inflammatory response. The specific role of this factor, however, had previously been unknown.
The researchers, led by Lee Quinton, PhD in the Department of Pathology and Laboratory Medicine at BUSM took models that possessed and lacked the STAT3 gene and created a model for pneumonia following sepsis. They first introduced a bacterial product that causes sepsis, followed by bacteria in the lungs to replicate pneumonia. Those lacking the gene had no difficulty dealing with simple pneumonia without sepsis. However, those infected initially with the sepsis model had higher bacterial burden from the pneumonia as well as higher mortality. The authors reasoned that this was due to the important role of STAT3 in promoting host defense, especially in the lungs.
Quinton recognizes that more research is needed to better understand the mechanism of the hepatic acute phase response, and how regulators such as STAT3 fit into the immune system as a whole. While it is still too early to determine clinical applications for patients, the authors are intrigued by the role of the liver in the protection against pneumonia, which is a common complication in septic patients. “A better understanding of how these distinct organs collaborate to mount immune responses has important clinical implications for patients with or at risk for pneumonia and sepsis. The idea that non-lung tissue could be targeted for treatments of lung disease is compelling,” said Quinton.
Funding for this study was provided by National Institutes of Health Grants R00-HL092956, R01-507 HL111449, R01-HL079392 and T32-HL007035.