Journal of Molecular Biomarkers and Clinical Trials

The Level of Regulatory T Lymphocytes may be Correlated with Outcomes in Early Sepsis

*Dr. Yih-Sharng Chen
Department Of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Province Of China

*Corresponding Author:
Dr. Yih-Sharng Chen
Department Of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Province Of China
Email:yschen1234@gmail.com

Published on: 2015-08-19

Abstract

Severe sepsis is associated with high mortality; however, the mortality of the secondary infection after severe sepsis is often higher than that of primary infection. A weaker pro-inflammatory response was found in survivors in primary inflection. The levels of pro-inflammatory cytokines in mid-term survivors, late death due to the secondary infection, were significantly higher than those in long-term survivors. Our hypothesis is that regulatory T cells (Tregs) suppress adaptive immune response in non-survivors and mid-term survivors. Therefore, the levels of Tregs between non-survivors and survivors, as well as between mid-term and long-term survivors in severe sepsis patients were examined to verify the hypothesis. Total 24 cases of severe sepsis, with outcomes of the early death (n = 5), mid-term survivors (n = 6), and long-term survivors (n = 13) were enrolled. The levels of lymphocytes, Tregs, monocytes, granulocytes, and neutrophil CD64 molecules were analyzed on days 0 (within 12 hours after the onset of the first organ failure due to sepsis), 1, 2, and 3 by flow cytometry and the levels of each variable were compared between groups by the mixed model. The recovery of lymphocytes was only observed The level of Tregs was significantly different between the early death and survivors, the early death and long-term survivors, in long-term survivors, as well as mid-term and long-term survival groups. The levels of neutrophil CD64 molecules indicated the ongoing infection. Results indicate that Tregs might affect immune homeostasis in patients with severe sepsis, influencing outcomes of early death, mid-term survival, and long-term survival.

Keywords

Severe Sepsis, Regulatory T Lymphocytes, Lymphocytes, Lymphocytopenia, Monocytes

Introduction

In intensive care units (ICUs), sepsis is one of the main causes of death and is often diagnosed on the basis of clinical symptoms, laboratory examinations, and lymphocytopenia [1]. The mechanism of systemic infection-induced lymphocytopenia is not clear. Microorganism infection induces not only an inflammatory response but also a release of anti-inflammatory factors, resulting in a heightened inflammatory reaction leading to early death, a balance between inflammatory and anti-inflammatory factors resulting in recovery [2]. Neutrophil CD64 molecules have been used as the indication of bacterial infection [3]. Our previous results indicate that a weaker pro-inflammatory response was found in survivors compared to non-survivors in the primary infection; furthermore, those died due to the secondary infection (mid-term survivors) did not have a more pronounced IL-10 response compared to long-term survivors in the early phase. However, the levels of pro-inflammatory cytokines between mid-term and long-term survivors were significantly different [4]. Immunoparalysis is considered as the main cause of the secondary infection in animal models [5]. No clinical evidence has been presented; furthermore, the duration of immune suppression is not known. We hypothesize that regulatory T cells (Tregs) suppress adaptive immune response in non-survivors, particularly for the late death from the secondary infection, see Figure 1. We measured the levels of lymphocytes, Tregs, monocytes, and granulocytes in severe sepsis patients to verify the correlation of Tregs to outcomes of early death, late death, and recovery. The ability to predict late death in the early phases of sepsis would help physicians develop new management strategies for these patients.