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

  • ️Fri Jan 01 2010

Comparative Study

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

Kevin R Kasten et al. BMC Immunol. 2010.

Abstract

Background: The 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.

Results: Neutrophil 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.

Conclusions: These 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.

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Figures

Figure 1
Figure 1

Human circulating neutrophil numbers and activation are both increased following blunt trauma. Results were obtained after collection of blood and flow cytometric analysis as described in the methods. (A) Absolute numbers of neutrophils are significantly increased following trauma. (B) Neutrophil activation is initially and remains increased following trauma. Data represents group size of 15 controls and 6, 7, and 9 blunt trauma patients at respective timeframes. *, p ≤ 0.05 versus controls. **, p ≤ 0.01. ***, p ≤ 0.001.

Figure 2
Figure 2

Oxidative burst increased in blunt trauma following fMLP stimulation. After specimen collection, neutrophils were stimulated and H2O2 production measured as described in the methods. (A) In comparison to controls, blunt trauma patients show increased oxidative burst activity. (B) Representative photographs of fMLP activated neutrophils were obtained demonstrating increased Dihydroxyrhodamine in a neutrophil from a blunt trauma patient at 48-72 h post injury. Data represents group size of 3 controls and 3 blunt trauma patients during the 48-72 h timeframe. *, p ≤ 0.05 versus controls. **, p ≤ 0.01.

Figure 3
Figure 3

Blunt trauma patients show increased percentage of activated CD11b within rafts, along with an elevated p-AKT. (A) CD11b rafts of blunt trauma patients demonstrate a higher percentage of CD11b within rafts relative to controls with similar results demonstrated by western blot. (B) Phosphorylated (p)-AKT following blunt trauma is markedly elevated compared to controls, while p-ERK and p-p38 are similar between groups. Data represents group size of 4 controls and 4 blunt trauma patients during the 48-72 h timeframe. *, p ≤ 0.05 versus control.

Figure 4
Figure 4

Human circulating T cell numbers are decreased following blunt trauma. Absolute numbers of (A) Naïve CD4, (B) Naïve CD8, (C) Effector CD4, and (D) Effector CD8 T cell populations were obtained by flow cytometric analysis as described in the methods section. Data represents group size of 15 controls and 6, 7, and 9 blunt trauma patients at respective timeframes. *, p ≤ 0.05 versus controls. **, p ≤ 0.01.

Figure 5
Figure 5

IFN-γ production decreased in trauma patients. Peripheral leukocytes were collected and then stimulated with cross-linked, soluble anti-CD3 and anti-CD28. After 48 hours, the cell culture supernatant was collected with IFN-γ concentration determined by ELISA. Data represents group size of 11 controls and 9 blunt trauma patients at 48-96 h post injury. *, p ≤ 0.05 versus controls.

Figure 6
Figure 6

The degree of CD247 phosphorylation is associated with bifurcated IFN-γ production in blunt trauma patients. Representative flow cytometry (A) of CD247 phosphorylation in controls versus trauma patients with low and normal IFN-γ production. Mean fluorescence intensity (MFI) of CD247 phosphorylation (B) in control patients versus low-IFN-γ producers and normal IFN-γ producers. Data represents group size of 11 controls and 4-5 blunt trauma patients at 48-96 h post injury. *, p ≤ 0.05 versus controls.

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