Elsevier

Cytokine

Volume 88, December 2016, Pages 214-221
Cytokine

Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with post traumatic sepsis

https://doi.org/10.1016/j.cyto.2016.09.010Get rights and content

Highlights

  • The skewing of the ratio of Th17/Treg along with Th2/Th1 may contribute to the pathogenesis of sepsis in THS patients.

  • T cell anergy, depressed Th1 cytokine production and skewing toward increased Th2 type immune reactivity may be a cause of poor outcome in THS patients.

Abstract

Introduction

Multiple organ dysfunction syndrome (MODS) developed due to the insult of trauma is a leading cause of death. The high mortality rate in these patients with and without sepsis has been reported up to 50%, throughout the world and thus required an urgent insight to overcome this problem.

Objective

The aim of this study is to examine the differential changes in subsets of T cells, imbalance in cytokine profile, immune-paralysis (T cell anergy) in Trauma hemorrhagic shock (THS) and post traumatic sepsis patients.

Methodology

114, THS patients and 50 healthy controls were recruited in the present study. We have measured the T cell proliferation assay using dominant antigens of both gram positive (LTA, 100 ng/ml) and gram negative (LPS-100 ng/ml) bacteria and PHA (4 μg/ml) using radioactive thymidine (1H3) assay. Simultaneously, we have measured the culture supernatant level of cytokines using Cytokine bead assay (CBA). The other parts of this study include the analysis of different subsets of T cells.

Results and conclusion

We observed significantly (P < 0.05) reduced T cell proliferation in THS patients as compared to control. Our study also showed patients died due to sepsis/septic shock, had significantly (p < 0.05) lower T cell response and had significantly elevated levels of IL-4, IL-10 and TGF-β, but low level of IL-2 and IFN-γ in culture supernatant. THS patients who developed sepsis complication had significantly higher T regulatory cells and lower Th17 cells in comparison to non-sepsis.

In conclusion, our study showed an imbalance in cell mediated immune response and disturbance in Th1/Th2/Th17 and T reg population of T helper cells and also the shifts towards Th2 and T17 in THS patients who had developed sepsis and showed poor outcomes.

Introduction

Now a days, a significant source of morbidity and mortality for all age groups particularly of young trauma patients are due to Trauma hemorhhagic shock (THS) related death and disability [1]. The main therapeutic concern of THS patients for the physicians is to stop bleeding as quickly as possible at the acute phase of haemorrhage. THS is a pathological state in which oxygen are not properly delivered to the different tissues of the body and intravascular volume reduced. If bleeding are not controlled in these patients that leads to the various complications such as hypoxia, inflammation, and organ dysfunction due to impairment of oxygen delivery. The early procedure involves to overcome the problem associated with trauma are fluid resuscitation, use of vasopressors, and blood transfusion to prevent or correct traumatic coagulopathy [2]. Trauma mortality is classically described as a tri-modal distribution of death: Immediate death are due to trauma on the spot, early death are due to uncontrolled systemic inflammatory response syndrome (SIRS) and imbalance in the production of inflammatory factors such as cytokines, chemokines, complement, oxygen radical, eicosanoids and nitrogen oxide and late death are due to multiple organ failure (MOF) [3]. Those THS patients, who survive the initial hours, have a greater risk of additional life-threatening complications, including uncontrollable infection (sepsis) and MOF [4].

Data from various sources revealed that despite of good hospitality and effective treatment, the mortality rate has not improved over the past few decades. So, if trauma patients survive early because of massive haemorrhage, they are at risk to develop complications like sepsis, septic shock and MOF later [5], [6]. The outcome is not determined only by trauma, but also by the intensity of the immune-inflammatory response, which is essential for host defense, but if uncontrolled leads to multiple organ dysfunction syndrome (MODS). The management of severely injured and multiple trauma patients are challenging for the physician because of the elicited immune response in these patients in the ICU. Subsequent life-threatening post traumatic complications such as severe sepsis, septic shock and MOF are associated with overproduction of pro-inflammatory mediators such as cytokines, chemokines and the critical disparity of cell-regulated innate immunity. In prolonged deregulated immune cell homeostasis, the immunological sequelae commonly develop either a state of hyper inflammation or immune suppression or both, and ultimately leading to MODS or lethal failure (MOF) [2].

According to present clinical and research evidences, there is no specific intervention for the MODS [7]. Early detection and prevention from MODS is therefore vital. According to a literature review among clinical research an India, there was no previous study in major traumatic injury patients focused on the evaluation of markers which predicts the early causes of MOF. The aim of present study was to compare prospectively the degree of activation of the immune-inflammatory cascade and also to correlate the expression of different subsets of T cells with a severity score of the patients who had developed sepsis or septic shock. In addition to this, the aim of our study was to understand the cause of T cell anergy in trauma patients and their relationships with severity of injury and their clinical outcomes and to evaluate the predictive value of these markers for the MOF and mortality.

The results from this study may provide crucial information on early detection of factors which affect the incidence of MOF. Accordingly, suitable preventative measures can be implemented in patients with severe injury with high quality care.

Section snippets

Patient characteristic

The human ethics committee, AIIMS, New Delhi (India) has approved the present study. Patients suffering from trauma, haemorrhage (n = 114) who were hospitalized in the Emergency Department of Trauma Centre, AIIMS between January 2011 and January 2014 were recruited. Eligibility criteria for enrollment in this study included the hemorrhagic shock patients of either sex by age 16–60 years with systolic blood pressure (⩽90 mmHg), presenting within 8 h of trauma after taking proper consent from the

Outcome and clinical variables

A total of 130 patients were enrolled in this study. Out of 130 patients, 16 patients were excluded from the analysis those who did not fulfilled the selection criteria or patients were resuscitated with colloids or crystalloids before reporting to the Emergency Department. Healthy volunteers (n = 50), including 38 men and 12 women (mean age, 32.6 ± 17.06 years) were included. Out of 114 patients, 77 (67.5%) survived and 37 (32.5%) died within one month in the hospital after injury. Out of 37 death

Discussion

The inflammatory cells and their associated mediators are obligatory in the pathological process of sepsis in THS patients. Regardless of extensive studies on these cells and mediators in both humans and mice, the pathogenesis of sepsis/septic shock remains poorly understood [10], [11]. It has recently been suggested that T lymphocytes subsets, especially CD4+ T helper cells contribute to the advancement of autoimmune and inflammatory diseases, including ARDS [12], [13]. But the potential role

Conclusion

In conclusion, the present study describes imbalance in Th17 cells and Treg cells in the peripheral blood of patients with sepsis and higher ratio of Th17 and Treg cells may be associated with poorer prognosis.

Declaration of interest

The authors have no conflicts of interest.

Acknowledgements

This work was funded through the Indian Council of Medical Research (ICMR), New Delhi. Author is thankful to the University Grant Commission (UGC), New Delhi, India for fellowship assistance. The excellent scientific assistance of Dr. Vinay, Dr. Amit Gupta and Dr. Arul Selvi is acknowledged.

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