Testing a new treatment target for sepsis

Vascular-Immune axis in sepsis: Nociceptin as an immune derived vasodilator

Although sepsis begins with infection, it can very quickly escalate to a severe immune reaction and circulatory problems. Blood pressure falls, and vital organs shut down because they do not receive the blood they need. Professor Lambert and his team believe that a molecule called nociception, produced by immune cells during sepsis, can cause the blood vessels to relax, and could underlie the dangerous drop in blood pressure seen in the condition. They have previously shown that levels of this molecule are higher in the blood of people who have sepsis, and other researchers have shown that nociceptin makes sepsis worse in animals. In this project, the team will simulate sepsis in human immune cells grown in the lab. They will measure how much nociceptin is produced using a novel ‘biosensor’, and determine which type of immune cells are making it. They will then test how this molecule affects the contraction and relaxation of human blood vessels, which is required to maintain a healthy blood pressure. If nociceptin is shown to have an important role, this could pave the way to develop drugs to block its effects, and potentially prevent dangerous drops in blood pressure and organ damage in sepsis.