Effect of severity of injury on immune system and its role in patient outcome in patients with Blunt Trauma to the chest
Authors: Kabiraj Pranay , Mathur Purva , Rajput Nigam , Priyadarshini Pratyusha , Kumar Abhinav , Alam Junaid , Choudhary Narendra , Bagaria Dinesh , Aggarwal Richa , Soni Kapil Dev , Madan Karan , Sagar Sushma , Gupta Amit , Mishra Biplab , Kumar Subodh 
Published: April 2024

BACKGROUND
Chest injuries are one of the most common injuries which are admitted in the trauma and emergency departments. It is known that the immune system affects the outcome of patients with significant trauma though the specific role of the components of immune system still remains to be explored. This study aimed to explore the temporal association of immune system with severity and development of complications in patients with blunt chest trauma (BCT).
METHODS
75 patients (50 non-intubated and 25 intubated) satisfying the inclusion and exclusion criteria were enrolled in the study and blood samples were collected on Day 0, Day 2, Day 5 and On the day of discharge. Broncho- alveolar lavage fluid was collected once in the intubated patients. The samples were processed to estimate the levels of intracellular cytokines of Neutrophils, T-regulatory cells and T-helper cells. Extracellular levels of IL-9, IFN-γ, TNF-α, IL-4, IL-22, IL-1β, IL-17A, IL-6, IL-10, TGF-β were estimated in the serum as well as in the BAL fluid. 30 healthy volunteers and 10 patients with esophageal cancer undergoing routine bronchoscopy without tracheobronchial involvement were used as controls. The levels of cytokines were compared between 1) the injured and healthy patients 2) patients with Injury severity Score <15 and >15 3) Patients with thoracic trauma severity score <5 and >5 , 4) patients who had uneventful recovery and patients who had uneventful recovery
RESULTS
Intraneutrophilic levels of IL-6((p<0.001**) ,IL-1β((p<0.001**) , Th22(p=0.0001), Th1(p=0.0012), Intracellular T-reg cytokines levels of IL-10(p=0.0001) and FOX-P3(p<0.001) levels were higher in the patients group as compared to the control group on day-0 of injury. Extracellular cytokines levels of TNF-α (p=0.0433), TGF-β (p=0.0069) were significantly raised in the patient group.
In the BAL fluid sample intraneutrophilic levels of IL-6(p<0.001), IL-1β(p<0.0002), Th22(p=0.016) and Th1(0.0049), Intracellular T-reg cytokines levels of TGF-β(p=0.0004) and FOX-P3(p=0.0003) were significantly increased in the patient group as compared to the control group. Extracellular levels of IL-4 (p=0.0271) and IL-1β (p=0.0041) were significantly elevated in the BAL fluid of patients.
Patients with overall higher injury severity score (ISS>15) had significantly increased intraneutrophilic cytokines as compared to those with ISS<15. The intracellular T-regulatory cytokines and intracellular T helper cell cytokines did not show such consistent significant results. The extracellular cytokines levels also did not show any statistically significant results in severely injured patients as compared to lesser injured group(ISS>15 vs ISS<15)
When compared on the basis of thoracic trauma severity intraneutrophilic cytokines levels did not show any significant results in patients with TTSS>5 vs TTSS<5. Intracellular T-regulatory cytokine levels of IL-10(p=0.0154), TGF-β(p=o.0006), FOX-P3(0.0001) were significantly increased in TTSS>5 group on the day of discharge. The extracellular levels of IL-9, IL-1β, IL-17A, IL-6, IL-10, and TGF-β were significantly elevated in TTSS >5 group even on the day of discharge.
Out of 75 patients 22 (29.33%) developed complications. In the complications group the intraneutrophilic cytokines levels of IL-6(p=0.0251) and IL-1β(p=0.0143) were significantly higher on the day of admission as compared to patients who did not develop any complications. The extracellular cytokines levels showed higher values on day 2 of injury of which IFN-γ(p=0.0022), TNF-α(0.0062), IL-4(p=0.0128), IL-1β(p=0.0241), IL-17A(p=0.0035), IL-6(p=0.0279) and IL-10(p=0.023) were raised significantly on day 2 in complications group as compared to patients without complications.
CONCLUSIONS
The immune system plays a very significant role in final outcome of patients with chest injury in addition to the anatomical injury. The severity of injury activates the immune system in a proportional manner and further exploration of this role can help in development of prognostic indicators and therapeutic immunomodulation.