Immunomodulation in transfused trauma patients

Abstract

Purpose of review: Traumatic injury is a major human health problem, with many injured people supported by transfusion of allogeneic blood. Although trauma and transfusion have both been known to have immunomodulatory effects for some time, little is known about their combined effects or the scope and kinetics of such responses.

Recent findings: Traumatic injury has a profound immunomodulatory effect on the patient, affecting a broad array of immunological components. This can be further complicated by transfusion, though the contribution of transfusion relative to the massive response triggered by trauma is small. The response to trauma involves a strong immunosuppressive component, which, contrary to the systemic inflammatory response syndrome/compensatory anti-inflammatory response syndrome model, occurs at the earliest time points examined and overlaps with proinflammatory and antimicrobial elements. This response is remarkably similar in a wide range of patients with different types and severities of injury.

Summary: The response to trauma and transfusion involves a massive and rapid reorganization of the immune system that can put the patient at increased risk of infection, tissue damage, and organ failure. The scope of the response presents challenges to the development of treatments to control this dysregulation.

Figure 1. Kinetics of immune response to trauma

Multivariable generalized estimating equations models were generated using the natural log of the concentration of each protein as the dependent variable and time since trauma, ISS, injury type, size of transfusion, age, sex, and microchimerism as the independent variables. Overlays of the models’ predictions of the influence of time since trauma controlling for the other covariates are plotted by protein type. Predicted values at 1 year after trauma are set as the baseline (0) for each cytokine to show elevation or depression relative to this value. The inflammation plot includes the pro-inflammatory cytokines IL-1α, IL-5, IL-9, IL-17, TNFα, TNFβ, and macrophage migration inhibitory factor (solid lines), the anti-inflammatory cytokines IL-1Ra and IL-10 (dashed lines), and IL-6, which has both pro- and anti-inflammatory properties (dotted line). The healing plot includes the wound healing proteins epidermal growth factor, fibroblast growth factor 2, vascular endothelial growth factor, matrix metallopeptidase 9, and total plasminogen activator inhibitor 1 (solid lines), the activated endothelial markers soluble E-Selectin, soluble intercellular adhesion molecule 1, and soluble vascular cell adhesion protein 1 (dashed lines), and the homeostasis cytokines IL-7 and IL-15 (dotted lines). (Adapted from Jackman, R. P., et al. 2012, Transfusion. doi: 10.1111/j.1537-2995.2012.03618.x)