Modifying Catabolic State:

The Steroids and Immunity from Injury through to Rehabilitation study (SIRS): This was our first observational study in both military and civilian patients examining the immune and endocrine response in severe trauma and long term outcomes. This was led by Prof Mark Midwinter and Lt Col Mark Foster and enabled us to set up our 24/7 research service for recruiting patients to trials. We have observed early release of immature neutrophils (white blood cells that engulf and kill bacteria) in the blood circulation of trauma patients; however these cells do not perform their function as well as mature neutrophils and may explain why trauma patients are more susceptible to infections/sepsis. To prevent the release of these defective cells novel drugs could be used targeted to e.g.heme oxygenase 1. This study has also revealed that in both young and old patients there is a dramatic loss of muscle in the first 2 weeks after injury. This correlates with almost complete loss of a steroid hormone “androgen Dehydroepiandrosterone (DHEA)” and its’ sulphated form DHEAS. A potential treatment would be to replace this by oral administration of DHEA. Currently we are designing a proof of concept study which, if successful, will lead to applying for competitive funding to perform a clinical trial.

Age is an important effect on outcome with the elderly having a poorer prognosis compared to young; it appears 50 years of age and above do worse. Following trauma the classical “pro-inflammatory” response is lower in older patients. Conversely the “anti-inflammatory” response is sustained in older patients for up to 6 months whereas in younger patients this is turned off by 4-6 weeks. Younger patients have better outcomes (reduced length of stay; infections; wound healing times). We have also looked at other markers – metabolites and are taking this forward with a small pilot grant where we are developing a diagnostic device to distinguish between sterile and non-sterile inflammation.