PCT和IL-6在感染性疾病中的诊断价值

目的：探讨血清降钙素原（PCT）与白介素-6（IL-6）在感染性疾病中的诊断价值。方法：采用罗氏全自动电化学发光免疫分析仪检测90例细菌感染性疾病、80例病毒感染性疾病和80例健康体检正常人血清PCT、IL-6含量,并对其结果进行分析。结果：细菌感染组PCT和IL-6含量显著高于病毒组及正常对照组,有显著性差异（P〈0.05）,病毒感染组PCT和IL-6含量与正常对照组比较无显著性差异（P〉0.05）,细菌感染组PCT和IL-6含量之间存在正相关性（P〈0.05）,病毒感染组PCT与IL-6含量之间无相关性（P〉0 05）,细菌感染组PCT、IL-6的阳性率显著高于病毒感染组及正常对照组,有显著性差异（P〈0.05）,病毒感染组PCT、IL-6阳性率与正常对照组相比无显著性差异（P〉0.05）,细菌感染组PCT的阳性率明显高于IL-6,有显著性差异（P〈0.05）。结论：IL-6在细菌感染中会出现阳性,但其不如PCT敏感,PCT检测是鉴别诊断细菌、病毒感染性疾病的良好指标。     

Usefulness of serum procalcitonin measurement in the diagnosis of bacterial infection in patients with systemic autoimmune diseases

Procalcitonin (PCT), a precursor for calcitonin, has been reported to be elevated in bacterial infection. However, its significance in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, who have treatment with corticosteroid and immunosuppressive drug, is limited. To investigate the usefulness of serum procalcitonin measurement in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, we analyzed 28 patients with systemic autoimmune diseases hospitalized because of fever and/or C-reactive protein (CRP) elevation. PCT was measured by the immunochromatography assay. Fourteen patients were considered having bacterial infections and the other 14 patients were considered having disease flare of their systemic autoimmune diseases. Serum CRP levels in the bacterial infection group was higher than that in the systemic autoimmune disease flare group; however, the difference did not reach statistical significance. The positive rate of serum PCT was significantly higher in the bacterial infection group (10/14, 71%) than that in the systemic autoimmune disease flare group (1/14, 7%), although there were 2 cases showing false positive PCT probably due to rheumatoid factor. This study suggested that PCT is useful in the diagnosis of bacterial infection in patients with systemic autoimmune diseases who are treated with corticosteroid and immunosuppressive drug.     

High-sensitivity C-reactive protein (CRP) assay--a novel method for assessment of risk ratios for atherosclerotic vascular diseases

CRP has long been used as a sensitive marker for infectious diseases. Since its serum concentration elevates more than 10 mg/dl with gram-negative bacterial infections, the sensitivity can be enough to be around 0.3-0.6 mg/dl for the diagnosis. However, the sensitivity should be higher in the early diagnosis of infections in new-borne babies. In addition, recently, it was suggested that atherosclerotic lesions are a kind of vasculitis, and the information could be transmitted via production of inflammatory cytokines and acute phase proteins. In fact, serum CRP and serum amyloid protein A(SAA) levels are elevated even in patients with coronary atherosclerosis without acute coronary syndrome(ACS). However, the level was much lower than the cut-off for diagnosis of bacterial infection. Therefore, the high-sensitive assay method has been applied. As the result, high-sensitivity(hs) CRP assay was found to be one of the most sensitive markers for prediction of future ACS in USA. Combination of hsCRP and atherogenic index such as total cholesterol/HDL cholesterol or LDL cholesterol/HDL cholesterol ratio is more useful. Similarly, it was found that hsCRP could predict the future prevalence of ACS even in Japan. It may be true because production of CRP is independent upon the genetic backgrounds. Early prevention of ACS by the measurement of hsCRP is calculated to be economic even if we measured hsCRF often in subjects without symptoms, because medical cost for treatment of acute myocardial infarction is enormous. In patients with high risk for coronary heart diseases, hsCRP-guided therapy is possible by using aspirin, stains, and antibiotics for prevention of ACS.     

Aggregation of white cells and C-reactive protein: relation between these two indices in acute phase reaction.

The association between aggregates of leucocytes in blood drawn from patients with various inflammatory conditions and the serum concentration of C-reactive protein (CRP) was examined: serum concentration of CRP might contribute to the development of cellular aggregations. A total of 213 patients with various inflammatory or necrotic conditions were examined (including 31 women with normal pregnancy and 59 controls). A significant correlation between the degree of leucocyte aggregation and CRP concentration was noted in patients with bacterial infections and in a group of patients with various inflammatory conditions. In contrast, there was no correlation between the extent of leucocyte aggregation and CRP concentrations in patients with viral infections, malignancies, or pregnancy. The presence or absence of aggregated leucocytes can help in differentiating between the respective bacterial or viral infections. The serum concentrations of CRP were increased in both types of infection, although when a quantitative CRP assay was used, considerably higher concentrations were detected in bacterial diseases.     

C反应蛋白和降钙素原与感染性疾病的相关性探讨

目的 探讨C反应蛋白（CRP）和降钙素原（PCT）的动态变化对感染性疾病的诊疗价值.方法 对细菌感染患者入院第2天,以及抗生素治疗第4天、第6天、第8天、第10天测定CRP、PCT水平动态变化,并作相关性分析.结果 85例患者入院第2天CRP、PCT水平均升高,随着感染控制CRP、PCT水平逐渐降低,第2天与第10天两者差异有统计学意义（P＜0.01）.结论 入院第2天有71例（占83.5％）患者CRP、PCT水平均明显升高.表明PCT特异性较好;治疗后期CRP仍然较高,但PCT已降至正常.     

C-reactive protein in acute viral infections

A sensitive solid-phase enzyme immunoassay procedure was used to determine the concentrations of C-reactive protein (CPR) in the acute and convalescent phase sera of patients with verified rubella, herpes simplex, cytomegalo, influenza A or B, enterovirus, or mycoplasma infection. In all infection groups about 90% (80% for influenza) elevated CRP values were observed in the acute phase sera (mean values in the different groups 16-57 micrograms/ml), the highest values exceeding or approaching 100 micrograms/ml. The serum CRP values were highest in all groups before the specific serum antibodies were detectable and decreased approaching the upper limit or normal controls (2 microgram/ml) within 2 weeks. Notable individual variation in the CRP production was seen. We conclude tha serum CRP determination should not be used as a reliable criterion to distinguish bacterial and viral infections.     

Efficacy of procalcitonin measurement in patients after total thyroidectomy due to medullary thyroid carcinoma

Procalcitonin (PCT) is a protein synthetized by the thyroid C cells, inside which it is cut into calcitonin (CT) and catacalcin. It remains undetectable in serum in normal conditions. Its level increases during inflammation and in small cell lung cancer. There have been studies suggesting that the PCT level increases in medullary thyroid carcinoma (MTC). So far there have been no reports that would assess the usefulness of PCT detection in MTC. Our aim was to evaluate the usefulness of serum PCT assays in patients with MTC. We investigated 24 patients at 17-78 years of age, all after total thyroidectomy due to MTC. All patients had serum CT concentrations measured by radioimmune assay. The upper limit of the CT level was 60 pg/ml. The serum PCT was evaluated with an immunochromatographic kit. The reaction was considered positive when the PCT level exceeded 0.5 ng/ml. In all cases the C-reactive protein (CRP) serum level was measured. The statistical analysis was performed with Statistica 5.1G. The CT levels in all patients varied from 0 to 1410, mean 603.8 pg/ml. In 8 patients the CT level was within normal range, in 6 patients it was marginally, and in 10 patients markedly elevated. The PCT test was considered positive in 16 patients. There was correlation among serum PCT and CT concentrations (Spearman test, p<0.0001). The PCT levels varied considerably among patients with normal, marginally and markedly elevated CT levels (Kruskal-Wallis test, p=0.0013). All patients had normal CRP values. Fisher's exact test revealed a correlation between serum PCT and CT increase (p=0.04). Further studies on a larger group of patients should be considered; thus, the PCT assay can be considered useful in cases of unclear CT concentration.     

Serum procalcitonin for differentiating bacterial infection from disease flares in patients with autoimmune diseases

Early differentiation between bacterial infections and disease flares in autoimmune disease patients is important due to different treatments. Seventy-nine autoimmune disease patients with symptoms suggestive of infections or disease flares were collected by retrospective chart review. The patients were later classified into two groups, disease flare and infection. C-reactive protein (CRP) and serum procalcitonin (PCT) levels were measured. The CRP and PCT levels were higher in the infection group than the disease flare group (CRP,11.96 mg/dL ± 9.60 vs 6.42 mg/dL ± 7.01, P = 0.003; PCT, 2.44 ng/mL ± 6.55 vs 0.09 ng/mL ± 0.09, P < 0.001). The area under the ROC curve (AUC; 95% confidence interval) for CRP and PCT was 0.70 (0.58-0.82) and 0.84 (0.75-0.93), which showed a significant difference (P < 0.05). The predicted AUC for the CRP and PCT levels combined was 0.83, which was not significantly different compared to the PCT level alone (P = 0.80). The best cut-off value for CRP was 7.18 mg/dL, with a sensitivity of 71.9% and a specificity of 68.1%. The best cut-off value for PCT was 0.09 ng/mL, with a sensitivity of 81.3% and a specificity of 78.7%. The PCT level had better sensitivity and specificity compared to the CRP level in distinguishing between bacterial infections and disease flares in autoimmune disease patients. The CRP level has no additive value when combined with the PCT level when differentiating bacterial infections from disease flares.     

Antibody to serum amyloid A

INTRODUCTION: Serum amyloid A (SAA) is elevated in inflammatory states. While antibodies to CRP, the other major acute phase reactant, have been described, to our knowledge, antibodies to SAA have not. This study was therefore undertaken to determine whether antibodies to SAA could be detected in patients and whether these antibodies are associated with any disease, in particular inflammatory states, using CRP as a proxy for inflammation. METHOD: An ELISA technique was developed for the detection of antibodies to SAA. Specificity was demonstrated by inhibition. Serum from one hundred and thirty-eight patients sent to the Clinical Immunology Laboratory for CRP evaluations were tested for anti-SAA activity. Their charts were reviewed for clinical parameters, in particular for inflammation, to determine association. Patients were also divided into those with normal and elevated levels of CRP, as a proxy for inflammation. As a control we also studied 62 normals. RESULTS: The mean OD and 3 SD of the 62 normal blood bank donors for anti-SAA was 0.411 +/- 0.577. Thus for the purposes of this study 0.988 was determined as the cutoff between normality and abnormality. Sixty-one normals and 114 patients had "normal" levels. Elevated levels were observed in 24 patients and 1 normal. There was an association between elevated levels and aortic stenosis, deep vein thrombosis, and systemic lupus erythematosus, seizures, stroke, and atrial fibrillation. There was no association between anti-SAA levels and CRP levels. CONCLUSIONS: These results show that antibodies to SAA develop in some patients. There was some association with inflammatory cardiovascular diseases.     

Procalcitonin, a new marker for bacterial infections

Procalcitonin (PCT), the precursor protein of the hormone calcitonin, appears to be an early marker of the presence of severe systemic infection. High serum concentrations are associated with severe systemic bacterial, parasitic or fungal infections. In contrast, PCT is generally not induced by severe viral infections or inflammatory reactions of non-infectious origin. Hence, PCT can be used for differential diagnosis of bacterial and viral meningitis. PCT may be helpful in the differentiation between infectious and non-infectious origin of systemic inflammatory response syndrome (SIRS) and acute respiratory distress syndrome (ARDS), pancreatitis, cardiogenic shock and acute rejection of organ transplants. PCT monitoring may be useful in patients with high risk of bacterial infection (major surgery, trauma, immunocompromised patients). PCT is a very stable molecule in vitro, and its measurement requires only 20 ml of plasma or serum and can be done within 2 hours.     

C-reactive protein in patients with bacteremia

Quantitative measurement of C-reactive protein (CRP) in serum has been proposed as a sensitive and, for some populations, a specific indicator of infection. To determine whether early measurement of CRP in serum could differentiate patients with bacteremia from a control group of patients whose blood cultures yielded contaminants, we measured CRP concentrations quantitatively by rate nephelometry in serum samples that had been obtained from patients on the same day as blood samples that yielded bacteria or fungi. Of the 36 episodes of bacteremia, 3 (8.5%) occurred in patients with normal concentrations of CRP in serum and 2 (5.5%) in patients with minimally elevated levels. Of the 21 episodes associated with contaminated blood cultures, only 2 (9.5%) occurred in patients with normal CRP levels. Of the patients with marked elevations of CRP (greater than 10 mg/dl), 18 (86%) had infection, although not all of these patients had bacteremia. We conclude that a normal concentration of CRP in serum does not eliminate the possibility of bacteremia. Moderate elevations (1 to 10 mg/dl) of CRP levels are common in both patients with contaminated blood cultures and in those with bacteremia. If the CRP concentration in serum is greater than 10 mg/dl and if other causes of marked elevations of CRP levels are eliminated, CRP concentration in serum may be a relatively specific indicator of infection. However, elevations of CRP concentrations are neither completely sensitive nor specific for detecting infection in patients with bacteremia.     

Analysis of procalcitonin and CRP concentrations in serum of patients with chronic spontaneous urticaria

Background

Our previous findings showed the importance of analysing the peripheral markers of acute phase response (APR) activation, C-reactive protein (CRP) and IL-6 in the context of urticaria activity and severity. However, these biomarkers do not reliably differentiate between APR to infectious and the disease severity.

Aim

In order to investigate a possible association between the immune-inflammatory activation markers CRP and procalcitonin (PCT).

Methods

Serum PCT and CRP concentrations were measured in patients with CU of varying severity as well as in healthy subjects.

Results

Serum PCT and CRP concentrations were significantly increased in more severe CU patients when compared to healthy controls and mild CU, and within the CU population there was a significant correlation between concentrations of PCT and CRP. Serum PCT concentrations remained within normal ranges in most CU patients and were only slightly elevated in some severe CU cases.

Conclusions

PCT serum concentration may be only slightly elevated in some cases of severe CU. Upregulation of PCT synthesis accompanied by parallel changes in CRP concentration reflects a low-grade systemic inflammatory response in CU. PCT should be considered as a better marker than CRP to distinguish between APR to infection and an active non-specific urticarial inflammation.     

血清降钙素原在儿童发热性疾病中的应用价值分析

目的 探讨降钙素原对儿童发热性疾病早期诊断及鉴别诊断的应用价值。方法 选取2015年7月~2016年3月我院收治的发热患儿270例,其中细菌感染组80例,非细菌感染组130例,对照组（非发热性疾病患儿）60例,入院前1 d已全部行WBC+CRP检测,入院当天全部行PCT检测,对比三组检测结果。结果 细菌感染组外周血WBC+CRP水平高于对照组,差异有统计学意义（P＜0.05）。细菌感染组PCT水平均高于非细菌感染组及对照组,差异均有统计学意义（P＜0.05）。结论 血清PCT可作为早期诊断细菌感染的可靠指标,对儿童发热性疾病的鉴别诊断及抗生素的使用具有重要意义。     

血清降钙素原、超敏C反应蛋白及白细胞介素-6在小儿急性上呼吸道感染中的诊断价值

目的:分析降钙素原(PCT)、超敏C反应蛋白(hs-CRP)和白细胞介素-6(IL-6)在小儿急性上呼吸道感染(AURI)时血清水平变化及其临床诊断价值。方法:分别收集100例AURI患儿,分为细菌感染组和病毒感染组(各50例),采用ELISA和免疫比浊法测定其血清PCT、hs-CRP、IL-6等指标,分析两病例组间及与健康体检儿童组间差异,并绘制细菌感染组上述检测指标的ROC曲线,比较其临床诊断价值。结果:细菌感染组血清PCT、hs-CRP与IL-6水平明显高于病毒感染组及健康对照组,差异有统计学意义(P0.05);病毒感染组PCT、hs-CRP和IL-6水平与健康对照组之间差异无统计学意义(P0.05)。对诊断细菌性AURI,血清PCT的ROC曲线下面积最大;灵敏度、特异度、阳性似然比明显高于hs-CRP和IL-6,阴性似然比显著低于IL-6,差异均有统计学意义(P0.05)。结论:血清PCT与hs-CRP、IL-6比较,其对小儿细菌性AURI具有更高的诊断价值及早期诊断意义。     

PCT和CRP联合检测对儿童呼吸道感染的临床意义

目的 分析PCT和CRP联合检测对儿童呼吸道感染的临床意义。方法 回顾性分析2016年6月~2017年3月我院呼吸科300例呼吸道感染疾病患儿,根据临床诊断分为病毒感染组（126例）和细菌感染组（174例）,分析两组检测的PCT和CRP结果并计算其阳性率。结果 细菌感染组PCT阳性率为85.63%,CRP阳性率为67.82%;病毒感染组PCT的阳性率为29.37%,CRP阳性率为63.49%。细菌感染组PCT阳性率明显高于病毒感染组;细菌感染组CRP阳性率与病毒感染组无明显差异。结论 PCT在细菌感染阳性率优于CRP,二者联合检测鉴别诊断儿童细菌、病毒感染性疾病具有更高临床价值。     

血清IL-6、CRP和PCT水平对严重多发伤后MODS的预测价值

目的探讨多发伤患者外周血血清白细胞介素-6(IL-6)、C反应蛋白(CRP)和降钙素原(PCT)对多器官功能障碍综合征(MODS)的预测价值。方法 87例多发伤患者按治疗过程中有无发生MODS分为MODS组和非MODS组。采用ELISA法测定患者伤后第1、2、3、5、和7天血清IL-6和PCT的含量,采用免疫比浊法测定血清CRP的水平,并与20例健康对照比较,应用受试者工作特征曲线(ROC曲线)进行统计学分析。结果与健康对照组相比,多发伤患者血清IL-6、CRP和PCT水平伤后早期均出现不同程度的升高(P<0.01),其中PCT水平升高最早;与非MODS组比较,MODS组各项指标均有显著差异(P<0.01)。IL-6、CRP和PCT的ROC曲线下面积分别为0.686、0.854和0.914。PCT对严重多发伤后发生MODS的诊断价值高于IL-6和CRP。结论 PCT是严重多发伤后预测MODS发生的较好辅助诊断指标,其诊断价值优于IL-6和CRP。     

Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats

Gram-negative and gram-positive infections have been considered the most important causes of morbidity and mortality in patients with leukopenia following chemotherapy. However, discrimination between bacterial infections and harmless fever episodes is difficult. Because classical inflammatory signs of infection are often absent and fever is frequently the only sign of infection, the aim of this study was to assess the significance of serum interleukin-6 (IL-6), IL-10, macrophage inflammatory protein-2 (MIP-2), procalcitonin (PCT), and C-reactive protein (CRP) patterns in identifying bacterial infections during start of fever in normal and cyclophosphamide-treated (leukopenic) rats following an injection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP) as a model for gram-negative and gram-positive bacterial infections. We found that, compared to normal rats, immunosuppressed animals exhibited significantly higher fevers and lesser production of all mediators, except IL-6, after toxin challenge. Moreover, compared to rats that received MDP, both groups of animals that received an equivalent dose of LPS showed significantly higher fevers and greater increase in serum cytokine levels. Furthermore, in contrast to those in immunocompetent rats, serum levels of IL-6 and MIP-2 were not significantly changed in leukopenic animals after MDP injection. Other serum markers such as PCT and CRP failed to discriminate between bacterial stimuli in both groups of animals. These results suggest that the use of the analyzed serum markers at an early stage of fever could give useful information for the clinician for excluding gram-negative from gram-positive infections.     

Intérêts du dosage de procalcitonine en infectiologie

Interest of procalcitonin assay in case of infections diseases. In 70 % healthy adults (n = 258 age range 19–95 years), PCT serum concentrations were below the detection limit of the immunoluminometric assay (< 0.08 ng/mL). In 30 % healthy patients, PCT serum levels were low : 0.08–0.25 ng/mL. A prospective clinical study was performed to assess the accuracy of procalcitonin (PCT) in 162 patients with fever on admission to the hospital. 43 patients had PCT Values superior to 0.5 ng/mL. High PCT (> 5 ng/mL) was found in patients with severe acute bacterial infections. In 17 patients with viral meningitis PCT higher level was 0.33 ng/mL. Chronic non bacterial inflammation does not induce PCT, serum concentrations were < 5 ng/mL. PCT determination seem to be diagnostic tools of differentiations between bacterial infections with systemic reactions of the organism, (excluding patients with medullary thyroïd carcinoma) to viral infections, and non bacterial inflammation. PCT was a good marker to control the success of a therapeutic procedure.     

Acute meningitidis,acute phase proteins and procalcitonin

The prognosis of bacterial meningitis is critically dependent on a rapid causal diagnosis and implementation of an accurate treatment. However, clinical and biological parameters available within the few hours that follow the patient's admission are not reliable enough, except when bacteria are to be found in cerebrospinal fluid under the microscope. Therefore, the initial treatment of acute meningitis is still most of time presumptive so that the definitive diagnosis, however difficult, is often established when the therapeutic management has already been initiated. The use of biological markers, especially lymphokines and acute-phase proteins, has been proposed to facilitate the accuracy of the initial diagnosis. Today, C-reactive protein (CRP) is the most widely used inflammatory marker in emergency departments with aim to discriminate bacterial from viral infections. In 1998, Gerdes et al. published a meta-analysis from 35 studies questioning the usefulness of CRP in discriminating bacterial meningitis from viral meningitis. They outlined that the majority of authors proposed to use this inflammation marker as an additional tool for discriminating bacterial meningitis from viral meningitis, without having evaluated its independent contribution relative to other parameters such as white blood cell count, cerebrospinal fluid (CSF) white cell count, protein or glucose. Procalcitonin (PCT) is an acute-phase protein with faster kinetics than CRP, its concentration in serum rising within the few hours that follow the inception of a bacterial infection. Two French studies published in 1997 and 1998 have shown that, using a cut-off range of 0.5 through 2 ng/mL, the sensitivity and specificity of PCT were 100% in discriminating bacterial meningitis from viral meningitis. Some of the seven studies published since seemed to demonstrate the usefulness of PCT in diagnosing meningitis. Finally, PCT was used effectively to shorten unnecessary antibiotic treatment for children seen in an hospital in Paris (France) during summer 2000.     

Systemic inflammation in cardiovascular and periodontal disease: comparative study

Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, alpha(1)-acid-glycoprotein (AAG), alpha(1)-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.