Elevated Serum Levels of Arachidonoyl-lysophosphatidic Acid and Sphingosine 1-Phosphate in Systemic Sclerosis

Systemic sclerosis (SSc) is an often fatal disease characterized by autoimmunity and inflammation, leading to widespread vasculopathy and fibrosis. Lysophosphatidic acid (LPA), a bioactive phospholipid in serum, is generated from lysophospholipids secreted from activated platelets in part by the action of lysophospholipase D (lysoPLD). Sphingosine 1-phosphate (S1P), a member of the bioactive lysophospholipid family, is also released from activated platelets. Because activated platelets are a hallmark of SSc, we wanted to determine whether subjects with SSc have altered serum lysophospholipid levels or lysoPLD activity. Lysophospholipid levels were measured using mass spectrometric analysis. LysoPLD activity was determined by quantifying choline released from exogenous lysophosphatidylcholine (LPC). The major results were that serum levels of arachidonoyl (20:4)-LPA and S1P were significantly higher in SSc subjects versus controls. Furthermore, serum LPA:LPC ratios of two different polyunsaturated phospholipid molecular species, and also the ratio of all species combined, were significantly higher in SSc subjects versus controls. No significant differences were found between other lysophospholipid levels or lysoPLD activities. Elevated 20:4 LPA, S1P levels and polyunsaturated LPA:LPC ratios may be markers for and/or play a significant role in the etiology of SSc and may be future pharmacological targets for SSc treatment.     

Increased Serum Levels of the IL‐33 Neutralizing sST2 in Limited Cutaneous Systemic Sclerosis

The pathophysiology of both limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous SSc (dcSSc), representing two subtypes of an autoimmune disease of the connective tissue, is still enigmatic. Life‐limiting, progressive fibrotic changes as a consequence of vasculopathy and autoimmunity are characteristic in varying extent for lcSSc and dcSSc. Previously, an increased IL‐33 serum concentration in early phase SSc patients and an elevated tissue expression of its receptor, ST2L, on endothelial cells (EC) were described. While suggested as a biomarker for fibrotic diseases, for example liver fibrosis, the role of soluble ST2 (sST2) in the pathological processes and its contribution to vascular fibrosis in SSc has not been investigated. Here, we showed that sST2 is elevated in late phase limited cutaneous SSc (lcSSc) as compared to patients with shorter disease duration or with the diffuse subtype of SSc. We demonstrated that sST2, not IL‐33, is significantly increased in serum of lcSSc patients with disease duration over 9 years. Soluble ST2 was not elevated in healthy controls or in SSc patients with early skin involvement or disease duration shorter than 9 years. Furthermore, we observed that sST2 serum levels were lowered by iloprost (prostacyclin) treatment. After 5 days of iloprost infusion, sST2 serum levels fell in 6 of 7 patients. Therefore, we not only like to propose sST2 as a biomarker for progressive vascular fibrosis, but moreover, suggest that the involvement of sST2 in the pathogenesis of lcSSc may be exploited therapeutically.     

Levels of Interleukin-15-Expressing Blood Mononuclear Cells Are Elevated in Multiple Sclerosis

Interleukin-15 (IL-15) is a novel IL-2-like cytokine expressed by cells of the monocyte/macrophage and epithelial lineages. Cytokines might be involved in the pathogenesis of multiple sclerosis (MS). Using immunocytochemistry, we analysed spontaneous expression of IL-15 by peripheral blood (PB) and cerebrospinal fluid (CSF) mononuclear cells (MNC) from patients with MS, other neurological diseases (OND) and healthy controls. IL-15- positive peripheral blood mononuclear cells (PBMNC) were elevated in patients with MS compared to healthy controls (P < 0.05). The elevation of IL-15- positive PBMNC was restricted to patients with chronic progressive MS and not observed in patients studied during the relapsing-remitting phase of MS. The numbers of IL-15- expressing PBMNC correlated with the duration and disability of MS (r = 0.45, P < 0.001, and r = 0.39, P < 0.01, respectively). IL-15 was undetectable in CSF MNC, and ELISA showed low CSF levels of IL-15 in occasional patients with MS and OND. IL-15 is a potent growth factor for gammadelta T cells, but there was no correlation between IL-15 expression by PBMNC and percentage of gammadelta T cells in blood from the MS patients. Together, these data demonstrate that IL-15 expression by PBMNC is upregulated in the chronic stage of MS.     

Clinical Significance of Serum HMGB-1 and sRAGE Levels in Systemic Sclerosis: Association with Disease Severity

Introduction  The high mobility group box 1 protein (HMGB-1)/advanced glycation end products (RAGE) system is recently shown to play an important part in immune/inflammatory disorders. However, the association of this system in systemic sclerosis (SSc) remains unknown. Materials and Methods  To determine clinical association of serum levels of HMGB-1 and soluble RAGE (sRAGE) in patients with SSc, sera from 70 patients with SSc and 25 healthy controls were examined by enzyme-linked immunosorbent assay. Sera from tight-skin mice and bleomycin-induced scleroderma mice, animal models for SSc, were also examined. Skin HMGB-1 and RAGE expression was assessed by immunohistochemistry. Results and Discussion  Serum HMGB-1 and sRAGE levels in SSc were higher than those in controls. Similarly, HMGB-1 and sRAGE levels in animal SSc models were higher than those in control mice. SSc patients with elevated HMGB-1 and sRAGE levels had more frequent involvement of several organs and immunological abnormalities compared to those with normal levels. Furthermore, HMGB-1 and sRAGE levels correlated positively with modified Rodnan total skin thickness score and negatively with pulmonary function test. Conclusions  HMGB-1 and sRAGE expression in the sclerotic skin was more intense than normal skin. These results suggest that elevated serum HMGB-1 and sRAGE levels are associated with the disease severity and immunological abnormalities in SSc.     

PSS病人血清中IL－2、IL－4、IL－6水平的测定

本文用生物测定法技术检测了３０例进行性系统性硬化症（ＰＳＳ）患者血清中白细胞介素２（ＩＬ－２）、白细胞介素４（ＩＬ－４）、白细胞介素６（ＩＬ－６）的水平。结果表明：在ＰＳＳ患者血清中，ＩＬ－２、ＩＬ－４的检出率显著高于对照组，ＩＬ－６的检出率虽然高于对照组，但是在统计学上无显著差异。结果提示：ＩＬ－２、ＩＬ－４可能在该病的发病机制中起一定作用。     

Mycoplasma pneumoniae Infection Affects the Serum Levels of Vascular Endothelial Growth Factor and Interleukin-5 in Atopic Children

Purpose

Previous studies have outlined mechanisms by which Mycoplasma pneumonia (M. pneumonia) infection may promote allergic lung inflammation and airway remodeling, and increasing evidence from human studies suggests that atypical bacterial infections contribute to asthma exacerbation, chronic asthma, and disease severity with changes in cytokine expression. The present study evaluated changes in serum levels of vascular endothelial growth factor (VEGF) and interleukin (IL)-5 in atopic children with Mycoplasma pneumoniae pneumonia.

Methods

We recruited a total of 72 children with pneumonia. The patients were divided into 4 groups: atopic children with M. pneumonia pneumonia (group I, n=24), non-atopic children with M. pneumonia pneumonia (group II, n=23), atopic children with viral pneumonia (group III, n=13), and non-atopic children with viral pneumonia (group IV, n=12). Serum levels of IL-5, IL-13, VEGF, and tumor necrosis factor-α were measured at admission and at recovery using enzyme-linked immunosorbent assays.

Results

Serum levels of VEGF and IL-5 were elevated in group I compared with the other groups at both admission phase and clinical recovery phase. In group I, serum levels of VEGF and IL-5 were higher at recovery phase than at admission phase (VEGF: 1,102.2±569.4 vs. 874.9±589.9 pg/mL, respectively; IL-5: 150.5±63.9 vs. 120.2±46.7 pg/mL, respectively).

Conclusions

The serum levels of VEGF and IL-5 were more increased in atopic children with M. pneumonia pneumonia than in the other groups. In this group, the serum levels of VEGF and IL-5 were more increased at recovery phase than at admission phase. The results of this study suggest that increases in VEGF and IL-5 may contribute to the development of hypersensitivity during M. pneumonia infection. These cytokines may act through their respective pro-inflammatory pathways to aggravate the allergic status and induce airway hypersensitivity during M. pneumonia pneumonia in atopic children.     

抑郁症患者IL-2及sIL-2R的检测及临床意义

目的　探讨白介素 -2 ( IL-2 )及可溶性白介素 -2受体 ( s IL-2 R)在抑郁症发病中的作用及临床意义。方法　用酶联免疫吸附法检测 30例抑郁症患者和 30例正常人血清 IL-2及 s IL-2 R水平 ,并比较二者的差异。结果　抑郁症患者 IL-2及 s IL-2 R分别为 95 1 .2± 1 1 0 .5 ngl/L、( 389.6± 2 1 1 .1 ) U/ml,高于对照组的 384 .1± 72 .5 ng/L、2 83.6± 1 4 6 .7U/ml,二者比较差异有显著性 ( P<0 .0 1 )。结论　抑郁症患者 IL-2及 s IL-2 R水平增高。     

SSc治疗前后血浆血管内皮细胞活性因子测定的临床意义

目的：探讨血管内皮细胞活性因子和系统性硬皮病(SSc)的关系及其在临床治疗中的意义。方法：利用密度梯度方法检测循环内皮细胞记数(CEC),利用放射免疫分析检测血浆内皮素(ET)、血栓素B2(TXB2)、6-酮-前列腺素F1a(6-K-PGF1a),利用Griss方法检测血浆一氧化氮(NO)水平,利用酶联免疫法检测细胞间粘附分子-1(ICAM-1)、P选择素(P-S),本文对52例SSc病人作了治疗前后的血浆水平的检测。结果：所有SSc患者均存在高CEC、ET、ICAM-1、P-S血症,存在低NO、6-K-PGF1a血症。结论：血管内皮细胞活性因子的变化同SSc的发生发展密切相关,其血浆水平的检测有助于SSc发病机制的探讨．有助于SSc疗效的观察。     

Rabbit Antithymocyte Globulin Serum Levels: Factors Impacting the Levels and Clinical Outcomes Impacted by the Levels

Antithymocyte globulin (ATG) levels and clearance vary significantly among patients receiving the same weight-based dose of ATG. To date, ATG area under the curve (AUC), its determinants, and its impact on clinical outcomes have been examined in pediatric hematopoietic cell transplant (HCT) and adult nonmyeloablative HCT. Here we set out to examine ATG AUC in 219 uniformly treated adults undergoing myeloablative allogeneic HCT at our institution. Sera were collected for the determination of pre- or post-HCT ATG AUC. The lowest quintiles of pre- and post-HCT AUC were associated with inferior chronic graft-versus-host disease (GVHD) and relapse-free survival (cGRFS) and a higher risk of acute GVHD, respectively. The highest pre- or post-HCT ATG AUC quintiles were not associated with risk of death, nonrelapse mortality, or relapse. Factors most strongly associated with AUC were day –2 recipient absolute lymphocyte count, body mass index (BMI), and graft lymphocyte content. To achieve ideal pre-HCT AUC (avoiding low AUC to maximize cGRFS) in this HCT setting, ATG dosing will need to take into consideration recipient weight, BMI, and blood and graft lymphocyte counts. Further studies are required to develop a modern ATG dosing schema and to demonstrate that adjusting ATG dose to target a particular AUC is feasible and leads to improved outcomes.     

Plasma Homocysteine Levels, The Prevalence of Methylenetetrahydrofolate Reductase Gene C677T Polymorphism and Macrovascular Disorders in Systemic Sclerosis: Risk Factors for Accelerated Macrovascular Damage?

The purpose of this study was to investigate plasma homocysteine (Hcy) levels in patients with systemic sclerosis (SSc) and to study the association between plasma Hcy, C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), and the clinical manifestations in SSc. Associations of Hcy level, C677T MTHFR polymorphism, and macrovascular diseases were investigated in 152 patients with SSc and 58 controls. No significant differences in Hcy levels and MTHFR genotypes were found in SSc patients compared to controls or in SSc patients with limited cutaneous compared to diffuse disease. Significantly higher Hcy concentration was observed in patients with macroangiopathy/thromboembolic events compared to patients without such clinical manifestations (p?<?0.05). There was significant correlation between age and macrovascular disorders, between Hcy level and the disease duration (r?=?0.164; p?<?0.05). Seventy-one percent of patients with macrovascular disorders had MTHFR polymorphism. In addition, 45% of patients with hyperhomocysteinemia had pulmonary hypertension. The presence of MTHFR C677T mutation influences the incidence of macrovascular abnormalities in SSc patients. Elevated Hcy levels may be associated with disease duration and the evolution of macrovascular disorders and pulmonary hypertension in SSc.     

未服药抑郁发作患者血清血管内皮细胞生长因子、碱性成纤维细胞生长因子浓度及其影响因素

目的:探讨血清血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(FGF-2)在抑郁发作中的可能作用。方法:采用酶联免疫吸附法测定30例未服药抑郁发作患者及30例健康对照血清VEGF、FGF-2的浓度;以两样本t检验比较两组血清VEGF、FGF-2的水平;采用Pearson相关来分析抑郁发作组血清VEGF、FGF-2的影响因素。结果:1抑郁发作组血清VEGF[(697.9±132.9)ng/L]、FGF-2[(333.8±85.9)ng/L]的浓度均高于对照组[分别为(617.3±83.7)ng/L、(270.6±42.5)ng/L,P均0.05];2抑郁发作组血清VEGF的水平与年龄(r=-0.465,P=0.011)负相关,与疾病持续时间、体质量指数(BMI)、24项汉密尔顿抑郁量表(HAMD-24)总分、汉密尔顿焦虑量表(HAMA)总分、自杀意念自评量表(Sl OSS)总分无相关性(P均0.05);血清FGF-2水平与年龄、疾病持续时间、BMI、HAMD-24总分、HAMA总分、Sl OSS总分无相关性(P均0.05)。结论:血清VEGF、FGF-2的浓度升高可能与抑郁发作有一定的相关性。     

Interplay of Infections,Autoimmunity, and Immunosuppression in Systemic Lupus Erythematosus

Infectious agents are considered to be crucial environmental factor in the etiopathogenesis of systemic lupus erythematosus (SLE). Infections may serve as initial trigger to the development of autoimmunity and carry an overall greater risk of morbidity and mortality than the general population. Initial presentation of SLE can mimic infections, and in turn infections can mimic disease flares in established SLE. Infections due to predisposition by commonly used immunosuppressive therapies are a significant cause of morbidity and mortality. In this review, viral, bacterial, fungal, and parasitic infections that contribute to the etiology of SLE, potentially mimic or precipitate flares, create diagnostic dilemmas, complicate treatment, or protect against disease, are discussed. Infection risks of current immunosuppressive therapies used in the treatment of SLE are outlined. Strategies to prevent infection, including vaccines, prophylactic antibiotic therapies, toll-like receptor antagonism, and antioxidant treatment that may decrease disease burden and improve quality of life in lupus patients will be discussed.     

Serum Concentrations of Cyclooxygenase-2 in Patients with Systemic Sclerosis: Association with Lower Frequency of Pulmonary Fibrosis

Systemic sclerosis (SSc) is a multisystem disease in which interplay between inflammation, autoimmunity and fibrosis appears to play an indispensable role. Owing to the suggested role of cyclooxygenase-2 enzymes (Cox-2) in inflammation and fibrosis, we investigated their serum concentrations in SSc patients and their clinical and laboratory associations. Serum from 49 patients with SSc, 28 of whom had limited cutaneous SSc (lSSc) and 21 had diffuse cutaneous SSc (dSSc) subtypes, and from 27 healthy subjects were assayed for Cox-2 and TNF by enzyme-linked immunosorbent assay (ELISA). Demographic, clinical, autoantibodies and serological data were prospectively assessed. The analysis revealed that patients with lSSc had higher levels of serum Cox-2 than controls. Serum Cox-2 levels were increased in SSc patients with arthritis and digital ulcers; on the contrary, these were diminished in those with associated pulmonary fibrosis. An additional prospective large scale, longitudinal study should be carried out to support these findings and to reveal the mechanistic connections between Cox-2 levels and SSc disease manifestations.     

Elevated Serum Anti-Saccharomyces cerevisiae, Anti-I2 and Anti-OmpW Antibody Levels in Patients with Suspicion of Celiac Disease

OBJECTIVES: Expression of anti-Saccharomyces cerevisiae antibodies (ASCA) identifies patients and individuals at risk for Crohn's disease and has also been reported in 40-60% of celiac disease (CD) cases, suggesting a role of host response to enteric microbiota in the development of inflammatory lesions. In this prospective study in patients with suspicion of CD, we evaluate the frequency and association of ASCA to serological responses for other host microbial targets formally associated with Crohn's disease, including the Pseudomonas fluorescens associated sequence I2 and a Bacteroides caccae TonB-linked outer membrane protein, OmpW. METHODS: Small bowel mucosal biopsies were taken from 242 patients with suspicion of CD, their sera were tested for antibodies to tissue transglutaminase (tTG), ASCA, I2, and OmpW. Eighty adult healthy blood donors were used as controls. RESULTS: The diagnosis of CD was confirmed on biopsy in 134 cases. The occurrence of ASCA and I2 positivity was significantly higher in adult CD patients than in patients with non-CD disease. Anti-I2 levels in the sera were significantly higher in adult CD patients than in non-CD disease or the controls and anti-OmpW levels in CD and non-CD patients when compared to controls. Positive seroreactivity to OmpW seemed to increase with age. Of the CD patients, 90% were seropositive for at least one microbial antigen tested. CONCLUSIONS: This study demonstrates a mosaic of disease-related serological responses to microbial antigens in patients with CD. Immune responses to commensal enteric bacteria may play a role in the small intestine mucosal damage in CD.     

Serum Levels of Interleukins 2, 6 and 8, Soluble Interleukin-2 Receptor and Intercellular Adhesion Molecule-1 During Treatment with Interleukin-2 Plus Interferon-Alfa

In the present study we evaluated the haematological and immunological changes in 4 patients with advanced melanoma and 6 patients with advanced renal cell carcinoma treated with subcutaneous interleukin (IL)-2 and interferon (IFN)-alfa-2b. Serum samples taken before and during six weeks' courses of IL-2 plus IFN-alfa were assayed for the presence of IL-2, soluble IL-2-receptor (sIL-2R), soluble intercellular adhesion molecule-1 (sICAM-1), IL-6 and IL-8. In addition, whole blood counts were taken. Eosinophilia occurred in all patients, lymphocytosis in 8 patients. The higher maximum level of IL-2 during treatment seemed to be connected to longer survival: it was a median of 578 pg/ml in the patients with a median survival of 7 months, and 1025 pg/ml in the patients who survived a median of 15 months. Conversely, an increase in slL-2R was an unfavourable sign: it was a median of 8-fold and 3-fold in the patients with a median survival of 7 and 16 months, respectively. During treatment, sICAM-1 levels paralleled with those of slL-2R. There was major intraindividual and interindividual variation in serum IL-6 and IL-8 levels with no distinctive kinetic pattern. Thus, no definite conclusions could be drawn. However, it seems worthwhile to measure IL-2, slL-2R and sICAM-1 during immunotherapy; their prognostic value should be further evaluated in a larger patient population.     

Clinical Value of Serum HMGB1 Levels in Early Detection of Recurrent Squamous Cell Carcinoma of Uterine Cervix: Comparison with Serum SCCA,CYFRA21-1, and CEA Levels

Aim

To evaluate the clinical value of serum high mobility group box chromosomal protein 1 (HMGB1) levels in making the early diagnosis of recurrent cervical squamous cell carcinomas (CSCC) and compare it with the value of serum squamous cell carcinoma antigen (SCCA), cytokeratin fragment (CYFRA) 21-1, and carcinoembryonic antigen (CEA) levels.

Methods

Immunohistochemical staining of tissue from 64 patients with recurrent CSCCs, 72 patients with non-recurrent carcinoma, and 28 healthy participants was performed to determine the expression of HMGB1 protein. The serum levels of the 4 markers in 112 patients with recurrent CSCC, 174 patients with non-recurrent disease, and 128 healthy participants were measured by enzyme-linked immunosorbent assay. The receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated.

Results

Higher immunostaining score was found in recurrent CSCC tissue sections than in non-recurrent CSCC sections. Serum HMGB1 levels in patients with recurrent CSCC were significantly higher than in patients with non-recurrent disease and healthy controls. The AUC of HMGB1, SCCA, CYFRA21-1, and CEA was 0.816, 0.768, 0.703, and 0.625, respectively. HMGB1 had the best specificity and positive likelihood ratio (78.0% and 3.25, respectively), whereas SCCA had the best sensitivity and negative likelihood ratio (76.3% and 0.34, respectively). Parallel combined measurements increased the diagnostic sensitivity and serial combination increased the specificity. High serum HMGB1 levels were inversely correlated with disease-free survival (P = 0.009, Pearson χ² test) and overall survival (P = 0.018).

Conclusion

HMGB1 was overexpressed in recurrent CSCCs. Serum HMGB1 level could be a useful and specific marker for evaluating the disease recurrence and predicting prognosis in patients with CSCC. Serial combined measurements of serum HMGB1, SCCA, and CYFRA21-1 increased the diagnostic specificity, and parallel combined testing increased the diagnostic sensitivity.Cervical carcinoma, one of the most frequent malignant tumors of the female reproductive system, remains to be among the leading causes of cancer-related death among women globally (1,2). Approximately 30% of International Federation of Gynecology and Obstetrics (FIGO) stage IB2 to stage IV cases will ultimately recur, despite modern multimodality treatment (3,4). Mostly, recurrence and metastasis occur in the local cervix, pelvic wall, and retroperitoneal lymph node. It is difficult to distinguish those diseases, except local relapse from radiation reaction or organized lymphocyst. One of the methods to identify early recurrence and prolong overall survival is screening of asymptomatic patients (5). In clinical practice, some tumor markers which can improve the sensitivity and specificity of diagnosis and prognostic prediction of recurrent cervical cancer have been used (6-9). Although recent advances have revealed different pathways in cervical carcinogenesis, no biomarker has yet been found to be significantly associated with the disease recurrence or clinical outcome in cases of cervical cancer. Therefore, finding new serum tumor markers of recurrent cervical squamous cell carcinomas (CSCC) for evaluating the cut-off value has become a frequent subject of investigation in the recent years.Nuclear protein, high mobility group box-1 (HMGB1), has been found to play an important role in tumor development, growth, and spread. Increased expression of HMGB1 has been reported in several different tumor types, including breast carcinoma (10), colorectal cancer (11), prostate cancer (12), pancreatic cancer (13), and hepatocellular carcinoma (14). HMGB1 plays a role in metastasis development, and thus links it to poor prognosis in a variety of cancers (15). In this study, we hypothesized that patients with recurrent cervical cancer would overexpress HMGB1 in tissue and serum.     

血清PCT、IL-6、NT-proBNP、CTnI和D-D测定水平在急诊脓毒症患者早期诊断中的临床研究

目的 为了探讨急诊脓毒症患者早期诊断中测定血清降钙素原(procalcitonin,PCT)、白介素-6(interleukin-6,IL-6)、N端脑利钠肽前体(n-terminal pro B-type netriuretic peptide,NT-proBNP)、肌钙蛋白Ⅰ(cardiac troponin Ⅰ,CTnI)和D-二聚体(D-dimer,D-D)水平的临床意义.方法 采用化学发光免疫分析、超敏酶免疫分析和荧光免疫分析测定了急诊就诊患者439例,其中307例诊断为急诊脓毒症患者(包括236例严重脓毒症和71例脓毒症休克)和普通感染患者132例,以及86例正常对照组血清生物标志物(PCT、IL-6、NT-proBNP、CTnI和D-D)水平,并进行了对比性分析.采用受试者工作特征曲线(receiver operating characteristic curve,ROC曲线)分析PCT、IL-6、NT-proBNP、CTnI和D-D评估急诊脓毒症患者早期诊断的临床价值.结果 307例急诊脓毒症患者血清PCT、IL-6、NT-proBNP、CTnI和D-D水平较之86例正常对照组明显增高(P分别为＜0.001,＜0.001,＜0.01,＜0.001和＜0.001),并且随疾病严重程度而增高.132例普通感染患者血清PCT、NT-proBNP、CTnI和D-D水平正常(P均＞0.05),仅血清IL-6水平轻度增高(P＜0.05).ROC曲线对急诊脓毒症早期诊断预测的价值评估表明:五种生物标志物均具有急诊脓毒症早期诊断的价值,以PCT为最佳,其后依次为IL-6、NT-proBNP、CTnI和D-D.结论 生物标志物(PCT、IL-6、NT-proBNP、CTnI和D-D)是急诊脓毒症早期诊断和病情严重程度评估的有价值指标.     

Systemic Inflammation and Disseminated Intravascular Coagulation in Early Stage of ALI and ARDS: Role of Neutrophil and Endothelial Activation

To determine the existence of a close link between inflammation and coagulation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and to examine their prognostic value in the development of ARDS and clinical outcome, we made a prospective cohort study. The study subjects consisted of 57 patients: 19 patients with ARDS and 38 patients with ALI as defined by a Lung Injury Score of > or =2.5 and 1.0 to less than 2.5, respectively. According to the outcome, the patients were subdivided into the survivors and the nonsurvivors. Ten normal healthy volunteers served as control subjects. Plasma levels of soluble L-, P-, and E-selectins, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (sTM), and neutrophil elastase were measured within 24 h after the diagnosis of ALI or ARDS. The number of systemic inflammatory response syndrome (SIRS) criteria being met by the patients and the disseminated intravascular coagulation (DIC) scores were determined simultaneously. The number of SIRS criteria and the DIC scores of the patients with ALI or ARDS showed high values, and more than half of the patients were complicated by DIC. The levels of sL-selectin in both groups of the patients were significantly lower than those of the control subjects. All other soluble adhesion molecules, neutrophil elastase, and sTM in the patients with ALI and ARDS were markedly elevated than those in the control subjects. The levels sICAM-1, sVCAM-1, and sTM in the ARDS patients significantly increased compared with the ALI patients. The number of SIRS criteria and the DIC scores in the nonsurvivors showed higher values than those in the survivors. In addition, we found significant differences in the levels of soluble adhesion molecules, neutrophil elastase, and sTM between the survivors and the nonsurvivors. In conclusion, we found a concurrent activation of both inflammation and coagulation in the patients with ALI or ARDS. The results also suggest that systemic activation of inflammation and coagulation associated with endothelial injury has prognostic value for the development of ARDS and poor outcome.