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The prognostic value of serum PCT, hs-CRP, and IL-6 in patients with sepsis

  • Zou Suhua , Zhang Lefeng EMAIL logo , Chen Qingli and Wu Yueying
Published/Copyright: December 29, 2017
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Open Life Sciences
From the journal Open Life Sciences Volume 12 Issue 1

Abstract

Objective

To evaluate the prognostic value of serum procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in patients with sepsis.

Methods

Sixty-six patients with sepsis were recruited in the 6th affiliated hospital of Wenzhou Medical University from February 2012 to April 2016. According to status of death or survival within 4 weeks, the patients were divided into death group (n=14) and survival group (n=52). The serum PCT concentration on the day of hospitalization was measured by double antibody immunosorbent assay, hs-CRP serum level was measured by immunoturbidimetric assay, and IL-6 serum concentration was tested by enzyme-linked immunosorbent assay (ELISA) of the included 66 patients. Serum PCT, hs-CRP, and IL-6 were compared between the two groups. The prognostic performance of serum PCT, hs-CRP, and IL-6 in patients with sepsis was evaluated through sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC).

Results

The serum concentrations of PCT, hs-CRP, and IL-6 in the death group were significantly higher than those of the survival group on the day of hospitalization (P<0.05). The sensitivities of serum PCT, hs-CRP, and IL-6 to predict the mortality of septic patients within 4 weeks were 94.64%, 83.93%, and 82.14%, and the specificities were 73.33%, 64.29%, and 71.43%, respectively. The areas under the ROC curves were 0.88, 0.76, and 0.77.

Conclusion

The serum levels of PCT, hs-CRP and IL-6 were significantly elevated in the death group, which could be used as serological markers to predict the risk of death for sepsis patients within 4 weeks.

Keywords: procalcitonin; high-sensitivity C-reactive protein; interleukin-6; sepsis; diagnosis

1 Introduction

Sepsis refers to a systemic inflammatory response syndrome (SIRS) caused by infections. Clinical epidemiological data have shown that the incidence of severe sepsis around the world is up to 18 million cases annually [1,2]. In the U.S, the sepsis incidence rate is 750,000 annually and has an annual rise of 1.5%-8.0% [3]. Sepsis is highly dangerous and has a high fatality rate. Approximately 14,000 people around the world die from sepsis and its complications daily, while approximately 215,000 people in America die from sepsis and its complications each year. Despite having an extremely high mortality rate, sepsis has no established death risk prediction model with high specificity, sensitivity and simple procedures yet. Recent studies have shown that various serological markers, such as serum procalcitonin and high-sensitivity C-reactive protein, have high concentrations in the serum of sepsis patients and are correlated to the severity of sepsis [4,5,6]. Thus, this study adopted double antibody immunosorbent assay and immunoturbidimetric assay to detect the levels of serum procalcitonin, highly sensitive C-reactive protein, and interleukin-6 in sepsis patients and explore their application value in predicting the risk of death for sepsis patients within 4 weeks.

2 Materials and methods

2.1 Patients

A total of 66 sepsis patients admitted to the Emergency Department and ICU of the 6th affiliated hospital of Wenzhou Medical University from February 2012 to April 2016 were recruited and subsequently divided into death group (n = 14) and survival group n = 52) according to whether the patient died within four weeks or not. The patient inclusion criteria were: (1) All the patients met the diagnostic criteria developed by the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) for sepsis; (2) The patients were more than 18 years old; (3) Informed consent was obtained from all individuals included in this study. The patients exclusion criteria were: (1) The patients didn’t meet the diagnostic criteria of sepsis; (2) Patients with history of malignant carcinoma; (3) Patients who were HIV positive. Of these patients, 41 were male and 25 were female. The general characteristics of the two groups are demonstrated in Table 1.

Table 1

The general characteristics of the two groups

CharacteristicsSurvival group (n=52)Death group (n=14)t/x2P
Age(years)56.6±18.958.7±23.10.350.73
Gender0.040.85
Male32(61.5%)9(64.3%)
Female20(38.5%)5(35.7%)
Infection lesion0.560.98
Lung infection18(34.6%)5(35.7%)
Abdominal cavity infection14(26.9%)3(21.4%)
Septicemia9(17.3%)2(14.3%)
Intracranial infection6(11.5%)2(14.3%)
Urinary tract infection3(5.8%)1(7.1%)
Others2(3.8%)1(7.1%)
APACHE II score15.6±6.222.4±8.14.410.001

2.2 Instruments and reagents

PCT double antibody immunosorbent assay kit was purchased from bioMéiieux Shanghai Biotech Co., Ltd. Hs-CRP immunoturbidimetric assay kit was purchased from Biosource America Inc. IL-6enzyme-linked immunosorbent assay kit was purchased from Biosource America Inc. AU5800 type automatic biochemical analyzer was purchased from Beckman Coulter, Inc. A blood cell analyzer was purchased from Beckman Coulter, Inc.

2.3 Detection of serum PCT, hs-CRP, and IL-16

On the 1st day of hospitalization, 5mL blood was sampled from each patient under fasting condition and then centrifuged to separate the serum, which was stored at –20 °C for further use. The serum PCT levels on the day of hospitalization were measured by double antibody immunosorbent assay, Hs-CRP serum level was measured by immunoturbidimetric assay, and IL-6 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Detection was performed strictly in accordance with the instructions of the kits.

2.4 Statistical analysis

Spss 17.0 software was used to do the statistical analysis. The measurement data were expressed with (χ ± S) and the comparison between groups was made by Student’s t-test. The enumeration data was expressed by a relative number, and the comparison between groups was made based on the χ2 test. The diagnosis sensitivity, specificity, and the area under the ROC curve were calculated according to the Bayes’ theorem. The statistical chart was drawn by GraphPad Prism 6 software. P<0.05 meant statistical difference.

Informed consent

Informed consent has been obtained from all individuals included in this study.

Ethical approval

The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

3 Results

3.1 Serum PCT, hs-CRP, and IL-6 level of the two groups

The serum level of PCT, hs-CRP, and IL-6 in the death group were significantly higher than that of the survival group on the day of hospitalization (P<0.05), Table 2, Figure 1.

Table 2

Serum PCT, hs-CRP, and IL-6 level comparisons between the two groups (χ ± S)

GroupPCT(μg/L)hs-CRP(mg/L)IL-6(ng/L)
Death (n=14)8.98±4.4571.54±20.5332.08±10.00
Survival (n=52)2.73±1.5253.44±13.9122.45±6.14
t8.573.884.51
P<0.01<0.01<0.05

Figure 1 Scatter plot of serum PCT, hs-CRP, and IL-6 levels of death and survival groups (A: serum PCT, B: serum hs-CRP, C: serum IL-6)
Figure 1

Scatter plot of serum PCT, hs-CRP, and IL-6 levels of death and survival groups (A: serum PCT, B: serum hs-CRP, C: serum IL-6)

3.2 Prognostic value of serum PCT, hs-CRP, and IL-6 in sepsis patients

The sensitivities of serum PCT, hs-CRP, and IL-6 to predict the mortality of septic patients within 4 weeks were 94.64%, 83.93%, and 82.14%. Whereas the specificities were 73.33%, 64.29%, and 71.43%, respectively (Table 3). The areas under the ROC curves were 0.88, 0.76, and 0.77 (Figure 2).

Table 3

Prognostic value of serum PCT, hs-CRP, and IL-6 in sepsis patients

ItemsAUC95%CIP valueCut-off valueSensitivitySpecificity
PCT0.880.76-0.99<0.015.24μg/L94.64%73.33%
hs-CRP0.760.61-0.91<0.0566.73 mg/L83.93%64.29%
IL-60.770.63-0.94<0.0527.68 ng/L82.14%71.43%

Figure 2 ROC curve of serum PCT, hs-CRP, and IL-6 in predicting deaths of sepsis patients
Figure 2

ROC curve of serum PCT, hs-CRP, and IL-6 in predicting deaths of sepsis patients

4 Discussion

At present, the mortality rate of sepsis remains as high as 30%-70% despite the considerable progress in anti-infective treatment and organ function support technology [7]. Sepsis treatment is highly expensive and consumes a considerable number of medical resources, and thus the disease seriously affects the quality of human life and poses great threat to human health [8]. Early diagnosis and intervention of sepsis have an important effect on the prognosis of sepsis patients [9,10]. Precise assessment of the severity of the disease, prediction of the risk of death at an early stage, and timely intervention can reduce the risk of sepsis turning into Multiple Organ Dysfunction Syndrome (MODS), further improve the recovery rates of the patients, reduce the risk of death, and decrease medical costs [11,12].

Despite having an extremely high mortality rate, sepsis has no established death risk prediction model with high specificity and sensitivity and simple procedures. Biochemical markers have been increasingly used in early diagnosis, management, and prognosis of sepsis. The ideal biochemical marker prognostic model should meet the following characteristics: has a simple method for measurement that can be widely used in clinical practice, enables clinicians to quickly intervene to improve prognosis, and can provide even better prognostic information than critically ill disease score. Recent studies [13,14,15,16] have shown that various serological proteins, such as serum procalcitonin, highly sensitive C-reactive protein, and interleukin, have high levels in the sera of sepsis patients and are correlated with the severity of sepsis. In particular, Li Zhenyu et al. [17] detected levels of serum procalcitonin, C-reactive protein, lactic acid, interleukin-6, and interleukin-10 in patients with sepsis and found that the levels of these substances in patients who died within 28 days were significantly higher than those who survived within 28 days. Furthermore, they used logistic regression to explore the independent risk factors of prognosis and discovered that PCT and IL-6 were the independent risk factors for patients who died within 28 days.

In our present study, we found that on the day of hospitalization, the PCT, hs-CRP, and IL-16 levels in the death group patients were significantly higher than those in the survival group. The sensibility values of the PCT, hs-CRP, and IL-6sera predicting death within 4 weeks were 94.64%, 83.93%, and 82.14%, respectively, and their corresponding specificities were 73.33%, 64.29%, and 71.43%, respectively. The areas under the ROC curve were 0.88, 0.76, and 0.77. These results showed that the PCT, hs-CRP, and IL-6 levels significantly increased in patients who died within 4 weeks and can thus be used as serum markers for the prediction of death risk.

Therefore, we conclude that the detection of serum procalcitonin, highly sensitive C-reactive protein, and interleukin-6 has certain predictive value for the prognosis and risk of death in sepsis patients. Furthermore, the detection procedures for these indicators are simple and practicable and thus meet the basic requirements for a promising biochemical marker prognostic model. However, the small sample size and patient inclusion from one hospital may lead to weak statistical power and patient selection bias. So, more prospective clinical studies or high quality meta-analysis of prognostic value of serum PCT, hs-CRP, and IL-6 in patients with sepsis are needed for further evaluation of its clinical usefulness.

  1. Conflict of interest: Authors state no conflict of interest.

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Received: 2017-8-24
Accepted: 2017-10-10
Published Online: 2017-12-29

© 2017 Zou Suhua et al.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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https://doi.org/10.1515/biol-2017-0050
Keywords for this article
procalcitonin; high-sensitivity C-reactive protein; interleukin-6; sepsis; diagnosis
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