Postoperative systemic inflammatory dysregulation and corticosteroids: a narrative review

Figure 1. Post‐traumatic dysregulated inflammatory‐immune state. Paradigm shift in the nature of the systemic inflammatory‐immune response to trauma based on analysis of differential gene expression. Initial rapid upregulation of proinflammatory genes involved in the innate immune response is accompanied by simultaneous downregulation of genes involved in adaptive immunity. Dysregulation of the host response is reflected by excessively altered gene expression for a prolonged period associated with complicated outcomes. Adapted with permission from reference [13] Creativecommons license by‐nc‐sa/3.0/.

Figure 2. The inflammatory‐immune response to surgical injury. (1) The host response is primarily driven by damage that is apparent at a molecular level; (2) danger‐associated molecular patterns (DAMPs), sensed by cells of the innate immune system, proliferate the response and activate the adaptive immune system further bolstering cell‐mediated immunity; (3) the response is balanced with the actions of interleukin 6 (IL‐6) driving the initial host response and simultaneously contributing to immune regulation and suppression; (4) Transition towards resolution and clearance is marked by a switch within inflammatory neutrophil lipid mediator (LM) biosynthesis pathways away from strongly chemoattractant and proinflammatory leukotrienes to lipoxins (Lipoxin A), proresolving LMs (resolvins and protectins) and resolving proteins (annexin 1). Monocyte‐derived macrophages reprogramme to a resolving macrophage (RM) promoting neutrophil apoptosis and tissue repair; (5) patient and surgical factors combine with intra‐operative events to escalate the response resulting in a pathophysiological state of immune imbalance and postoperative systemic inflammatory dysregulation (PSID); (6) this response may…

Figure 3. Unified model of glucocorticoid mediation of the immune response. Hypothetical timeline of the immune response to surgery in the presence (red) and absence (blue) of glucocorticoids as proposed by Cain and Cidowoski, based on the biphasic action of glucocorticoids. At low levels, glucocorticoids promote expression of innate immune genes and a rapid initial response to surgical injury. Postoperatively, the stress response and/or corticosteroid supplementation suppresses signalling and inflammation promoting resolution and restoration of homeostasis. When there is an absence or relative lack of glucocorticoid (adrenalectomy or antagonism), the initial response is delayed and the duration of the response is prolonged. Adapted with permission from reference [80].