Sepsis is a highly dangerous inflammatory reaction to infection involving the whole body. Once it strikes, sepsis can cause significant drops in blood pressure, endothelial cell damage, and systemic organ failure. Because all systems and organs are at risk of infection, the morbidity and mortality rates are high. The Center for Disease Control and Prevention estimates over 750,000 cases of sepsis per year.
To beat sepsis successfully is to diagnose it as early as possible. To date, there is no detection method to cue doctors of imminent sepsis. But the National Institute of Health recently awarded the Ford research team $1.78 million to develop a sepsis diagnostic tool that’s based on a new lipid biomarker.
The biomarker is called chlorinated lipids, referring to the “bleached” effect of these molecules. In immune cells, inflammation triggers a massive release of oxidants, one of which is cellular bleach. Invading germ cells are subsequently killed by the chlorinating, or bleaching, effects of these oxidants. However, as collateral damage, some host cells, namely lipids, are also chlorinated by the oxidants.
The Ford team discovered these chlorinated lipids in their lab for the first time in 2002. The molecule had never before been identified in people, but the team quickly showed that the body does indeed produce these specially marked lipids. Most crucially, they showed that chlorinated lipids only get made under conditions of infection or inflammation. Therefore, these molecules can be used as the biomarker equivalent of the “canary in the coal mine,” alerting doctors to the threat of sepsis quickly and accurately.
To test their theory, the Ford team assembled a 3-prong approach in collaboration with two other research teams. Specifically, the research will heavily focus on how chlorinated lipids affect endothelial cells and mediate organ failure. Endothelial cells make up the circulatory lining of every tissue in the body, so understanding how chlorinated lipids alter these cells is crucial to developing an accurate biomarker for sepsis. Through additional cellular and animal studies, the teams hopes to determine whether the presence of chlorinated lipids can serve as "indicators of disease severity, organ failure, or clinical outcome for septic patients.""I hope that we find a valid biomarker. We could improve therapy for sepsis before detrimental outcomes occur." Dr. David Ford
The teams will spend the next few years understanding chlorinated lipids in order to develop a suitable biomarker test for sepsis."If we can catch it earlier, we are in a much better position to treat sepsis before it gets too bad. This a case where 12 or 24 hours can make a big difference." Dr. Jane McHowat, collaborator on the grant.
To learn more about sepsis, watch the follwing short animation.
Sources: Grantome, Eurekalert