Explaining Cause Of Fatal Inflammatory Response
A new study is giving medical researchers new insight into a cellular injury that leads to unexplained inflammation, extended hospital stays and increased mortality in intensive care units.
The study examined the causes of systemic inflammatory response syndrome (SIRS), a bodily reaction to injury or illness that occurs in approximately one-fifth of patients admitted to intensive care units, and is associated with approximately 25 percent mortality.
The study conducted by critical care researchers at Ohio State University Medical Center found that necrosis, or unregulated cell death, leads to the activation of monocytes, or mononuclear inflammatory cells, through the release of factors normally found in specialized energy-producing organelles called mitochondria.
The research is currently available online and will be published in the June issue of the journal Critical Care Medicine.
“Our study shows that specific mitochondrial components trigger a potent immune response. This observation provides novel insight into the mechanisms linking cell damage to inflammation in the context of acute illness,” says Dr. Elliott Crouser, a pulmonologist and critical care specialist at Ohio State’s Medical Center, and first author of the study.
Mitochondria, which have many features of their bacterial ancestors, normally avoid contact with immune cells due to their intracellular location. However, when cells or tissues are damaged, which occurs during various acute illnesses, mitochondrial elements are commonly released and cause the immune system to become highly activated. But exactly what triggers this robust inflammatory response is not understood.
“Mitochondrial injury likely represents a critical ‘hit’ to the body not only by injuring its ability to generate energy supplies, but also by releasing these mitochondrial products that can prolong the SIRS process,” says Dr. Mark Wewers, also a pulmonologist and critical care specialist at OSU Medical Center, and senior author of the study.
Blood monocytes from healthy human adults were incubated with necrotic cell components or with specific mitochondrial proteins, and analyzed for immune cell activity. Researchers confirmed their hypothesis that the mitochondrial component of damaged cells triggers immune cell activation. The scientists also identified some of the mitochondrial components that are capable of activating immune cells.
“Early responses to sepsis, and ultimately SIRS, are driven by the body’s ability to immediately sense the infectious agent and send out danger signals to hormones responsible for acute fever and blood pressure problems,” adds Wewers. “The ‘late’ component to SIRS appears to be a marker for prolonged illness and the severity of the response, and a better understanding of this response will provide specific novel treatment options for preventing SIRS.”