Sepsis is a leading cause of morbidity and mortality for children worldwide. The majority of children who die of sepsis suffer from refractory shock and/or multiple organ dysfunction syndrome (MODS) within the initial 72 h of the treatment[8, 9]. In addition, sepsis has a prolonged hospitalization duration and high treatment costs, are major concerns to human health[8, 9]. Therefore, early identification and appropriate resuscitation and management are critical to optimizing the outcomes for children with sepsis. In this study, we demonstrated that the levels of BCL-xL, but MMP-index and TNF-α, were significantly correlated with disease severity (SNAP II).
The BCL-xL belongs to the Bcl-2 family and regulates cell apoptosis. In the presence of an apoptosis signal, BCL-xL is translocated to the mitochondrial outer membrane. Also, it is distributed on the cytoplasm and membrane in normal conditions. BCL-xL inhibits not only cell apoptosis but also cell necrosis. It is a protective protein against cell damage induced by an inflammatory response in the body.
In a study of adult sepsis, the content of BCL-xL and platelet MMP in patients with septic shock was decreased at the same time as compared to those with sepsis, which indicated that the mitochondrial function was severely damaged, and the normal oxidative phosphorylation of the cell could not be carried out. This resulted in a critical state of the body, which was in agreement with the critical disease score. Currently, there are no data on the BCL-xL serum content. We speculated that the expression of BCL-xL protein in the cells was enhanced under the stimulation of inflammatory factors before sepsis. However, after the cells and mitochondria were severely damaged and could not maintain normal morphology and function, the generated BCL-xL protein was released into the blood. Therefore, we aimed to provide effective and reliable molecular biological indicators for clinicians to assess the degree of damage and the severity of the disease and predict the disease progression through the detection of BCL-xL level in the blood of newborns with sepsis. In this study, the level of BCL-xL was significantly correlated with disease severity, reflecting the interaction between external damage and the body, as well as the severity of the disease. Both the sensitivity and specificity of the BCL-xL were in distinguishing sepsis shock. The blood BCL-xL content is expected to be a new molecular marker to identify sepsis shock early.
A correlation has been established between SNAP II and neonatal prognosis. In this study, SNAP II in the septic shock group was significantly higher than that in the sepsis group. Blood BCL-xL protein level was similar to that of SNAP-lI. These findings suggested that the combination of BCL-xL and SNAP-II was more sensitive and specific than the BCL-xL to predict neonatal sepsis outcomes.
Sepsis is considered to be over-inflammation, followed by protracted inflammation and immune suppression. TNF-α regulates apoptosis by caspase-8 and Fas apoptotic pathway. Mitochondria constitute the central target in the apoptotic pathway leading to platelet apoptosis, and mitochondrial damage is an early indicator of cell death in platelets. A previous study demonstrated a correlation between platelet MMP-index and disease severity in ICU patients with Systemic Inflammatory Response Syndrome (SIRS). In this study, patients did not show a significant correlation between MMP-index and TNF-α with SNAP-II. SNAP-II has high sensitivity and specificity in predicting severity outcomes in neonatal sepsis[15, 16], but another study demonstrated that the value of SNAP-II was low for predicting mortality. In the current study, most cases were mild: 24 (64.9%) patients had SNAP-II < 20. Simonson et al. reported that at a cut-off value of ≥ 20 in the presence of sepsis, the SNAP-II score could predict the mortality outcome.
Nevertheless, the present study has several limitations. First, the sample size of 36 patients is small. Thus, large clinical trials are needed to confirm the current findings. Secondly, while most patients (73.0%) did not obtain an MMP-index, only 10 patients (27.0%) showed the index. This is due to the high requirement of the MMP-index examination of fresh blood specimens at the earliest. Many patients failed to achieve MMP because they missed the optimal examination time, which leads to the failure of experiments. The next step is to improve the detection rate of MMP-index.
We demonstrated that BCL-xL was enhanced in circulating platelets in patients with sepsis. Thus, the findings suggested that BCL-xL is associated with the progression of sepsis. The serum BCL-xL combined with SNAP-II could be early predicte the severity of the disease.