Immune capacity determines outcome following surgery or trauma: a systematic review and meta-analysis

Abstract

Purpose: Immunological functions are altered following physical injury. The magnitude of the immunological response is dependent on the initial injury. However, variability in the immune response exists within and between patients where only some patients are at risk of developing complications such as systemic inflammatory response syndrome after injury. This systematic review and meta-analysis assessed whether lipopolysaccharide (LPS) induced cytokine production capacity of leucocytes can be used as a functional test to predict the risk of developing complications after injury. Methods: Medline, Embase and Web of Science were systematically searched to identify articles that investigated the association between LPS induced cytokine production capacity in leucocytes and any clinical outcome after surgery or trauma. Where sufficient information was supplied, a meta-analysis was performed to determine the overall clinical outcomes. Results: A total of 25 articles out of 6765 abstracts identified through the literature search were included in this review. Most articles described a positive association between cytokine production capacity and the development of inflammatory complications (n = 15/25). Coincidingly, the meta-analysis demonstrated that TNFα (Hedges g: 0.63, 95% CI 0.23, 1.03), IL-6 (Hedges g: 0.76, 95% CI 0.41, 1.11) and IL-8 (Hedges g: 0.93, 95% CI 0.46, 1.39) production capacity was significantly higher, one day after injury, in patients who developed inflammatory complications compared to patients who did not following trauma or surgical intervention. No significant difference was observed for IL-1β. Conclusion: The associations of elevated LPS-induced cytokine production capacity with the risk of developing inflammatory complications are consistent with previous theories that proposed excessive inflammation is accompanied by anti-inflammatory mechanisms that results in a period of immunosuppression and increased risk of secondary complications. However, immunological biomarkers for risk stratification is still a developing field of research where further investigations and validations are required.