Divergent adaptive and innate immunological responses are observed in humans following blunt trauma

Abstract

BackgroundThe immune response to trauma has traditionally been modeled to consist of the systemic inflammatory response syndrome (SIRS) followed by the compensatory anti-inflammatory response syndrome (CARS). We investigated these responses in a homogenous cohort of male, severe blunt trauma patients admitted to a University Hospital surgical intensive care unit (SICU). After obtaining consent, peripheral blood was drawn up to 96 hours following injury. The enumeration and functionality of both myeloid and lymphocyte cell populations were determined.ResultsNeutrophil numbers were observed to be elevated in trauma patients as compared to healthy controls. Further, neutrophils isolated from trauma patients had increased raft formation and phospho-Akt. Consistent with this, the neutrophils had increased oxidative burst compared to healthy controls. In direct contrast, blood from trauma patients contained decreased naïve T cell numbers. Upon activation with a T cell specific mitogen, trauma patient T cells produced less IFN-gamma as compared to those from healthy controls. Consistent with these results, upon activation, trauma patient T cells were observed to have decreased T cell receptor mediated signaling.ConclusionsThese results suggest that following trauma, there are concurrent and divergent immunological responses. These consist of a hyper-inflammatory response by the innate arm of the immune system concurrent with a hypo-inflammatory response by the adaptive arm.

Early infection during burn-induced inflammatory response results in increased mortality and p38-mediated neutrophil dysfunction

“…Additionally, restricted resuscitation and support therapies in mice limit the severity of burn injury that can be inflicted. However, our "first hit" results are consistent with numbers and functionality changes seen in human blunt trauma patients (19). We did not use analgesia after inducing a scald burn injury in these mice, consistent with our previous work (44).…”

“…The phenotypic findings that we observed in scalded mice on PBD1 were similar to the divergent and concurrent immune response seen in blunt trauma patients (19). After establishing a clinically relevant model, we hypothesized that the adverse response to infection in burn mice was related to temporal immunological changes.…”

“…Following trauma, the number and functionality of leukocytes are altered (19). The injury type, severity, and host genetic predisposition are key to changes in the immune status.…”

“…In the innate arm of the immune system, the inflammatory response involves increased neutrophil recruitment, activation, and functionality (19). Increased early peripheral leukocytosis with a subsequent decline to below sham levels has been demonstrated in a murine model of burn injury (4).…”

Interleukin-7 (IL-7) Treatment Accelerates Neutrophil Recruitment through γδ T-Cell IL-17 Production in a Murine Model of Sepsis

“…Further, it is known that T cells undergo apoptosis within the first 24 h after onset of sepsis (25,27,57), and the degree of apoptosis correlates with the sepsis severity (24,33). Additionally, remaining T cells demonstrate reduced functionality illustrated by decreased production of gamma interferon (IFN-␥) (28). Taken together, these results provide mechanistic insight into how prevention of T-cell apoptosis improves survival in a murine model of sepsis (26) and illustrate a therapeutic avenue for reduction of morbidity and mortality associated with this disease process.…”