Orexin as a Potential Drug for Treating Septic Shock

Article

Sepsis is a life-threatening condition due to excessive immune responses to infection that damages the patient's own tissues and organs. In septic shock, the severest stage of sepsis, the blood pressure drops to a dangerously low level, often leading to multiple organ failure and death. To date, there is no effective therapy yet available for septic shock. Recent findings by Japanese scientists may be a breakthrough in developing a silver bullet for the treatment of septic shock.

This is a hypothetical schema of multiple pathways by which OXA may improve survival in mice with LPS-induced endotoxin shock. Courtesy of University of Tsukuba
 
Sepsis is a life-threatening condition due to excessive immune responses to infection that damages the patient's own tissues and organs. In septic shock, the severest stage of sepsis, the blood pressure drops to a dangerously low level, often leading to multiple organ failure and death. To date, there is no effective therapy yet available for septic shock. Recent findings by Japanese scientists may be a breakthrough in developing a silver bullet for the treatment of septic shock.

The research team led by Yasuhiro Ogawa, Yoko Irukayama-Tomobe and Masashi Yanagisawa of the International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, found that subcutaneous injection of the neuropeptide orexin can markedly improve survival rate of mice suffering from endotoxin shock (sepsis model mice). Orexin, discovered by Yanagisawa and his colleagues in 1998, plays a critical role in controlling sleep/wakefulness, and is also known to alter heart rate and body temperature in rats, suggesting that it may potentially be a therapeutic agent for circulatory shock. However, the clinical application of orexin is technically difficult because it works in the brain, and delivery of orexin to the brain is hampered by the blood-brain barrier (BBB), an interface that selectively transports essential molecules to the brain and separates the brain from the circulatory system in order to protect the central nervous system (CNS) from hazardous substances.

"We exploited the leakiness of the BBB, a hallmark pathophysiology of the systemic inflammatory syndrome, in order to deliver orexin into the CNS," Irukayama-Tomobe says. The researchers confirmed that peripherally injected orexin can enter the brain because of the enhanced BBB permeability caused by septic shock, which subsequently helps mice to survive and recover from septic shock by restoring body temperature and increasing the heart rate. They further found that orexin is likely to regulate immune responses through multiple signaling pathways in the brain.

Future studies include elucidation of the precise mechanism through which CNS orexin regulates the responses of the immune system. They are validating the effect of peripherally administered orexin in primates with septic shock, aiming at clinical applications in the future.

Source: University of Tsukuba

Recent Videos
Pathogen Playbook Presenter: Sharon Ward-Fore, BS, MS, MT(ASCP), CIC, FAPIC
Mark Wiencek, PhD
Rebecca Crapanzano-Sigafoos, DrPH, CIC, AL-CIP, FAPIC
The CDC’s updated hospital respiratory reporting requirement has added new layers of responsibility for infection preventionists. Karen Jones, MPH, RN, CIC, FAPIC, clinical program manager at Wolters Kluwer, breaks down what it means and how IPs can adapt.
Studying for the CIC using a digital tablet and computer (Adobe Stock 335828989 by NIKCOA)
Infection Control Today's Conversations with the HSPA President, Arlene Bush, CRCST, CER, CIS, SME, DSMD, CRMST
Infection Control Today's Conversations with the HSPA President, Arlene Bush, CRCST, CER, CIS, SME, DSMD, CRMST
Cheron Rojo, BS, FCS, CHL,  CER, CFER, CRCST
Matthias Tschoerner, Dr Sc
Standardizing Cleaning and Disinfection
Related Content