Investigating Interleukin – 8 and TGF Beta as early biomarkers predicting poor clinical outcome in major trauma

Abbood, L 2021, Investigating Interleukin – 8 and TGF Beta as early biomarkers predicting poor clinical outcome in major trauma , MPhil thesis, University of Salford.

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Abstract

Trauma is a leading cause of death and disability. Globally, traumatic injury is the main cause of death under the age of 45. Recent studies from the UK report a demographic change in major trauma. The most common mechanism of traumatic injury is falling from less than 2 meters, with the primary demographic being elderly males. The imbalance between pro and anti-inflammatory immune states following trauma is postulated to cause an exaggerated compensatory anti- inflammatory response. This leads to an immuno-suppression and increased susceptibility to sepsis and multi-organ failure, thus contributing to the late phase deaths due to major trauma. Here where test the hypothesis that early cytokine changes defining these immune imbalances could be exploited as biomarkers to predict poor clinical outcomes and second phase deaths in major trauma. IL-8 as a pro-inflammatory cytokine and TGF-β as a pleiotropic cytokine with a potent regulatory activity were investigated for their potential as early biomarkers. The availability of such biomarkers will aid in patient stratification, thus enabling prioritisation of such patients for early, focused clinical and therapeutic interventions. The results will add to a larger multi-centric study looking at cytokine, cellular immune and metabolomic biomarkers as early predictors of poor clinical outcome in major trauma. Blood samples, clinical, biochemical and demographic data were collected for major trauma patients admitted to Central Manchester and Salford Royal Foundation Trusts on Day 1 and Day 5 post trauma (NIHR Portfolio study BIT 19377). IL-8 and TGF-β trends monitored using BD Biosciences cytometric bead arrays showed a steady, statistically significant decline from days 1- 5 post-trauma in the whole trauma cohort (IL-8 P=0.013; TGF-β P= 0.000). The high levels on Day 1 of both cytokines suggest the potential use of these cytokines as early biomarkers if they related to poor clinical outcome. In order to do this, the patient cohort (IL-8. n = 53; TGF-β, n = 38) was analysed based on calculated Sequential Organ Failure assessment SOFA scores on Day 1 and 5. A SOFA score of ≥3 was deemed as a cut off to denote early organ failure. IL-8 and TGF-β levels on Day 1 were compared in patients clustered based on SOFA scores (≥3 cut offs) on Day 5. While higher levels were observed for IL-8 and TGF-β on Day 1 for the poor outcome cluster (SOFA ≥3) than when compared to the good outcome control (SOFA <3) the values were not statistically significant (IL-8 p = 0.218 ; TGF- β p = 0.624). When the SOFA cut offs were increased to cluster on the basis of more severe organ failure (SOFA ≥ 6), the p values obtained were as follow; significant (IL -8 p = 0.894; TGF-β p = 0.075). While this is still not statistically significant, increase in the significance for TGF-β, when clustered with patients with more adverse outcomes is noteworthy and needs to be further evaluated in a larger cohort patient. The pleiotropic nature of TGF-β makes it harder to hypothesise whether a pro or anti-inflammatory mode of action is adopted in its response. The multifaceted role of this cytokine needs a better understanding of the function in combination with other immune modulatory factors by investigating the pattern of cytokine level along the acute period of trauma and during the recovery.

Item Type: Thesis (MPhil)
Contributors: Nirmalan, NJ (Supervisor)
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Depositing User: LUHAIB Abbood
Date Deposited: 05 Oct 2021 13:47
Last Modified: 05 Oct 2021 13:47
URI: http://usir.salford.ac.uk/id/eprint/61431

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