Peripherally administered orexin improves survival of mice with endotoxin shock

摘要

The body has a range of defenses to fight infection, which play a crucial role in keeping us healthy. However, sometimes the response to infection may damage the body’s own tissues and organs, leading to a life-threatening condition called sepsis. In the most severe stage of sepsis – known as septic shock – blood pressure drops to dangerously low levels and the individual often dies. There is currently no effective therapy for septic shock. Recent studies have revealed how the brain regulates immune responses via chemical signals and nerve impulses. A molecule called orexin is made in the brain and regulates the activity of a group of neurons that control sleep. Orexin can also alter heart rate and body temperature in rats, which suggests that it may have potential to be developed as a treatment for septic shock. To test this idea, Ogawa, Irukayama-Tomobe et al. injected orexin under the skin of mice with septic shock. The experiments show that the injected orexin is able to enter the brain, where it helps the mice to survive and recover from septic shock by restoring normal body temperature and boosting heart rate. Further experiments suggest that orexin is likely to regulate immune responses through multiple signaling pathways in the brain. The next step following on from this work is to find out the precise mechanism through which orexin regulates the responses of the immune system. This orexin treatment strategy should also be tested on primates with septic shock before planning any clinical trials in humans.