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Activation of anti-inflammatory systems following major trauma

Endogenous pro- and anti- inflammatory lipids in trauma

Principal Investigator: Professor Ben Ollivere

The project was awarded £14,800 from the University of Nottingham National Rehabilitation Centre and Faculty of Medicine and Health Sciences strategic funds via an open call held in March 2022.

The following activities were completed during the period April to July 2022:

Study Design

Serum samples were collected from healthy controls (n=78), multiple rib fracture patients (n=17) and frail hip fracture patients (n=32). Samples were collected pre-operatively (at time of anaesthesia) or in any case within 48 hours of admission to hospital. Control samples were collected from a cohort of healthcare workers from Nottingham.

LC-MS/MS Analysis

Pro- and anti-inflammatory lipid mediators were extracted from serum samples and measured by liquid chromatography-mass spectrometry using our in-house method in the School of Pharmacy. A total of 36 lipid mediators were quantified in serum samples.

Results

  • Most hydroxyeicosatetraenoic acids (5-HETE, 11-HETE, 12-HETE, 19-HETE) are significantly lower in trauma cases than in controls. This is common to both rib and hip fractures.
  • Anti-inflammatory compounds (precursors) in the sEH pathway are significantly less abundant in trauma samples relative to controls, particularly 11,12- EET and 14,15 EET.
  • Thromboxane B2 levels are significantly lower in trauma cases indicating problems with platelet aggregation.
  • Endocannabinoids are highly abundant in both types of trauma cases relative to controls. Importantly, in rib fractures (healthy, young trauma cases) 2-AG is the only EC that is significantly higher than controls. In hip fractures (frail, elderly, ~10% mortality within 6 months) OEA and PEA are in high abundance, AEA is significantly higher in hip than in rib fractures. These data indicate that the EC system is activated in response to trauma but the different patterns involved suggest different involvement of CB1, CB2 and TRPV1 in the two types of trauma cases.

Future Work

These data will be incorporated with other datasets collected from these participants, including proteomic measurements, for further analyses. The aim of these analyses will be to build up a larger picture of the ‘molecular signature’ of trauma.

These findings will also form the basis for future application to NIHR EME as it can be used as a tool to show efficacy of surgical and rehabilitation intervention in this patient population.