Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS

ObjectiveTriggering receptor expressed on myeloid cells-1 (TREM-1) was reported to play a key roll in amplification of production of inflammatory cytokines. TREM-1 is suggested to be a specific biomarker for sepsis for this reason, but the clinical significance of TREM-1 has not been elucidated. We investigated TREM-1 expression on the cell-surface, and plasma levels of soluble TREM-1 (sTREM-1) in patients with non-infectious systemic inflammatory response syndrome (SIRS) and sepsis admitted to the ICU.MethodsThirty-five patients with SIRS and 21 patients with sepsis admitted to ICU were subjected to the study. TREM-1 expressions on the surfaces of monocytes and neutrophils were measured by flow cytometry. Plasma sTREM-1 level and serum interleukin (IL)-6 level were measured.ResultsSeptic patients had decreased TREM-1 expression, clearly on neutrophils or to a lesser extent on monocyte compared to SIRS patients on ICU admission (neutrophils p < 0.001, monocyte p < 0.05). TREM-1 expression on neutrophils had a significant inverse correlation with serum IL-6 level (r = ?0.64, p < 0.0001). Plasma sTREM-1 level in septic patients was significantly higher than that in SIRS patients (p < 0.05). Plasma sTREM-1 level positively correlated with severity score and non-survivors had increased plasma sTREM-1 level compared to survivors in all SIRS/sepsis patients (p < 0.05).ConclusionsPatients with sepsis had increased soluble TREM-1 and decreased TREM-1 expression on neutrophil compared to SIRS patients. sTREM-1 may be useful to evaluate disease severity and outcome of patients with SIRS or sepsis.     

Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis

ObjectiveTriggering receptor expressed on myeloid cells-1 (TREM-1) is an important receptor involved in the innate inflammatory response and sepsis. We assessed soluble TREM-1 (sTREM-1) in 112 septic neonates (63 culture-positive and 49 culture-negative) and 40 healthy controls as a potential early diagnostic and prognostic marker for neonatal sepsis (NS).MethodsStudied neonates were evaluated for early- or late-onset sepsis using clinical and laboratory indicators upon admission. sTREM-1 was measured on initial sepsis evaluation and at 48 h after antibiotic therapy. For ethical reasons, cord blood samples were collected from control neonates and only samples from neonates that proved to be healthy by clinical examination and laboratory analysis were further analyzed for sTREM-1.ResultsBaseline sTREM-1 levels were significantly elevated in culture-proven (1461.1 ± 523 pg/mL) and culture-negative sepsis (1194 ± 485 pg/mL) compared to controls (162.2 ± 61 pg/mL) with no significant difference between both septic groups. Culture-positive or negative septic preterm neonates had significantly higher sTREM-1 compared to full term neonates. sTREM-1 was significantly higher in neonates with early sepsis than late sepsis and was associated with high mortality. sTREM-1 was significantly decreased 48 h after antibiotic therapy compared to baseline or levels in neonates with persistently positive cultures. sTREM-1 was positively correlated to white blood cells (WBCs), absolute neutrophil count, immature/total neutrophil (I/T) ratio, C-reactive protein (hs-CRP) and sepsis score while negatively correlated to gestational age and weight. hs-CRP and sepsis score were independently related to sTREM-1 in multiregression analysis. sTREM-1 cutoff value of 310 pg/mL could be diagnostic for NS with 100% sensitivity and specificity (AUC, 1.0 and 95% confidence interval [CI], 0.696–1.015) while the cutoff value 1100 pg/mL was predictive of survival with 100% sensitivity and 97% specificity (AUC, 0.978 and 95% CI, 0.853–1.13). However, hs-CRP cutoff 13.5 mg/L could be diagnostic for NS with a sensitivity of 76% and specificity of 72% (AUC, 0.762 and 95% CI, 0.612–0.925) and levels were not related to survival as no significant difference was found between dead and alive septic neonates.ConclusionsElevated sTREM-1 could be considered an early marker for NS that reflects sepsis severity and poor prognosis.     

Expression and Purification of a Functional Porcine Soluble Triggering Receptor Expressed on Myeloid Cells 1

Triggering receptor expressed on myeloid cells 1 (TREM-1) plays a vital role in the pathogen-triggered amplification loop required for proinflammatory responses. Blockade of TREM-1 signaling may inhibit expansion of sepsis and prolong survival of animals. In the present study, the gene of porcine soluble TREM-1 was cloned and expressed in E. coli. After purification, the bioactivity of recombinant porcine soluble TREM-1 was tested in vitro on porcine alveolar macrophages. The results showed that supplementation with the recombinant porcine sTREM-1 protein rapidly and dose-dependently attenuated the upregulation of cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12, IL-16, IL-18, and TNF-α) caused by LPS stimulation in the cultured porcine alveolar macrophages. These results indicate that the recombinant porcine sTREM-1 protein can prevent TREM-1-mediated hyperinflammatory responses after exposure to LPS.     

Pandemic Influenza (H1N1) 2009 Pneumonia: CURB-65 Score for Predicting Severity and Nasopharyngeal Sampling for Diagnosis Are Unreliable

Background

From the first case reports of pandemic influenza (H1N1) 2009 it was clear that a significant proportion of infected individuals suffered a primary viral pneumonia. The objective of this study was twofold; to assess the utility of the CURB-65 community acquired pneumonia (CAP) severity index in predicting pneumonia severity and ICU admission, and to assess the relative sensitivity of nasopharyngeal versus lower respiratory tract sampling for the detection of pandemic influenza (H1N1) CAP.

Methods

A retrospective cohort study of 70 patients hospitalised for pandemic influenza (H1N1) 2009 in an adult tertiary referral hospital. Characteristics evaluated included age, pregnancy status, sex, respiratory signs and symptoms, smoking and alcohol history, CURB-65 score, co-morbidities, disabling sequelae, length of stay and in-hospital mortality outcomes. Laboratory features evaluated included lymphocyte count, C-reactive protein (CRP), nasopharyngeal and lower respiratory tract pandemic influenza (H1N1) 2009 PCR results.

Results

Patients with pandemic (H1N1) 2009 influenza CAP differed significantly from those without pneumonia regarding length of stay, need for ICU admission, CRP and the likelihood of disabling sequelae. The CURB-65 score did not predict CAP severity or the need for ICU admission (only 2/11 patients admitted to ICU had CURB-65 scores of 2 or 3). Nasopharyngeal specimens for PCR were only 62.9% sensitive in CAP patients compared to 97.8% sensitivity for lower respiratory tract specimens.

Conclusions

The CURB-65 score does not predict severe pandemic influenza (H1N1) 2009 CAP or need for ICU admission. Lower respiratory tract specimens should be collected when pandemic (H1N1) 2009 influenza CAP is suspected.     

A Biomarker Panel (Bioscore) Incorporating Monocytic Surface and Soluble TREM-1 Has High Discriminative Value for Ventilator-Associated Pneumonia: A Prospective Observational Study

Introduction

Ventilator-associated pneumonia (VAP) increases mortality in critical illness. However, clinical diagnostic uncertainty persists. We hypothesised that measuring cell-surface and soluble inflammatory markers, incorporating Triggering Receptor Expressed by Myeloid cells (TREM)-1, would improve diagnostic accuracy.

Methods

A single centre prospective observational study, set in a University Hospital medical-surgical intensive Care unit, recruited 91 patients into 3 groups: 27 patients with VAP, 33 ventilated controls without evidence of pulmonary sepsis (non-VAP), and 31 non-ventilated controls (NVC), without clinical infection, attending for bronchoscopy. Paired samples of Bronchiolo-alveolar lavage fluid (BALF) and blood from each subject were analysed for putative biomarkers of infection: Cellular (TREM-1, CD11b and CD62L) and soluble (IL-1β, IL-6, IL-8, sTREM-1, Procalcitonin). Expression of cellular markers on monocytes and neutrophils were measured by flow cytometry. Soluble inflammatory markers were determined by ELISA. A biomarker panel (‘Bioscore’), was constructed, tested and validated, using Fisher’s discriminant function analysis, to assess its value in distinguishing VAP from non VAP.

Results

The expression of TREM-1 on monocytes (mTREM-1) and neutrophils (nTREM-1) and concentrations of IL-1β, IL-8, and sTREM-1 in BALF were significantly higher in VAP compared with non-VAP and NVC (p<0.001). The BALF/blood mTREM-1 was significantly higher in VAP patients compared to non-VAP and NVC (0.8 v 0.4 v 0.3 p<0.001). A seven marker Bioscore (BALF/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1β, and serum CRP and IL-6) correctly identified 88.9% of VAP cases and 100% of non-VAP cases.

Conclusion

A 7-marker bioscore, incorporating cellular and soluble TREM-1, accurately discriminates VAP from non-pulmonary infection.     

血清TRAF-6、MCP-1、sTREM-1、IL-33水平与脓毒症严重程度及与合并急性肾损伤关系的临床分析

目的:探讨脓毒症患者血清肿瘤坏死因子受体相关因子(Tumor necrosis factor receptor-related factor,TRAF)-6、单核细胞趋化蛋白(Monocyte chemotactic protein,MCP)-1、可溶性髓样细胞触发受体(Soluble myeloid cell trigger receptor,s TREM)-1、白介素(Interleukin,IL)-33水平的变化及与病情严重程度及合并急性肾损伤(acute kidney injury, AKI)的相关性。方法:选择2014年2月到2018年7月在我医院ICU病房进行诊治的脓毒症患者145例,分析脓毒症相关性急性肾损伤(sepsis-associated AKI,SAKI)的发生情况,比较SAKI和非SAKI患者血清TRAF-6、MCP-1、s TREM-1、IL-33水平,采用Pearson相关分析血清TRAF-6、MCP-1、s TREM-1、IL-33含量与APACHEⅡ评分、SOFA评分的相关性,多因素logistic回归分析脓毒症患者发生SAKI的影响因素。结果:在145例患者中,发生SAKI者69例,发生率为47.6%。SAKI组患者的年龄、性别、原发病、白细胞(white blood cell,WBC)计数、C反应蛋白(C reactive protein,CRP)、降钙素原(procalcitonin,PCT)、体重指数、BUN、Scr与eGFR值与非SAKI组患者对比差异均无统计学意义(P0.05)。SAKI组患者APACHEⅡ评分、SOFA评分血清TRAF-6、MCP-1、s TREM-1、IL-33含水平含量均显著高于非SAKI组患者(P0.05)。Pearson相关性分析显示血清TRAF-6、MCP-1、s TREM-1、IL-33水平与SAKI患者的急性生理和慢性健康Ⅱ(acute physiology and chronic health evaluation II,APACHEⅡ)评分、序贯多器官功能障碍(sequential organ failure assessment,SOFA)评分均呈显著正相关性(P0.05)。logistic回归分析显示血清TRAF-6、MCP-1、s TREM-1、IL-33水平升高均为影响SAKI发生的独立危险因素(P0.05)。结论:血清TRAF-6、MCP-1、s TREM-1、IL-33水平与脓毒症严重程度显著相关,可能作为诊断和治疗SAKI的参考指标及干预靶点。     

Severity of Influenza A 2009 (H1N1) Pneumonia Is Underestimated by Routine Prediction Rules. Results from a Prospective,Population-Based Study

Background

Characteristics of patients with community-acquired pneumonia (CAP) due to pandemic influenza A 2009 (H1N1) have been inadequately compared to CAP caused by other respiratory pathogens. The performance of prediction rules for CAP during an epidemic with a new infectious agent are unknown.

Methods

Prospective, population-based study from November 2008–November 2009, in centers representing 70% of hospital beds in Iceland. Patients admitted with CAP underwent evaluation and etiologic testing, including polymerase chain reaction (PCR) for influenza. Data on influenza-like illness in the community and overall hospital admissions were collected. Clinical and laboratory data, including pneumonia severity index (PSI) and CURB-65 of patients with CAP due to H1N1 were compared to those caused by other agents.

Results

Of 338 consecutive and eligible patients 313 (93%) were enrolled. During the pandemic peak, influenza A 2009 (H1N1) patients constituted 38% of admissions due to CAP. These patients were younger, more dyspnoeic and more frequently reported hemoptysis. They had significantly lower severity scores than other patients with CAP (1.23 vs. 1.61, P = .02 for CURB-65, 2.05 vs. 2.87 for PSI, P<.001) and were more likely to require intensive care admission (41% vs. 5%, P<.001) and receive mechanical ventilation (14% vs. 2%, P = .01). Bacterial co-infection was detected in 23% of influenza A 2009 (H1N1) patients with CAP.

Conclusions

Clinical characteristics of CAP caused by influenza A 2009 (H1N1) differ markedly from CAP caused by other etiologic agents. Commonly used CAP prediction rules often failed to predict admissions to intensive care or need for assisted ventilation in CAP caused by the influenza A 2009 (H1N1) virus, underscoring the importance of clinical acumen under these circumstances.     

Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide-stimulated human monocytes

Triggering receptors expressed on myeloid cell (TREM) proteins are a family of cell surface receptors that participate in diverse cellular processes such as inflammation, coagulation, and bone homeostasis. TREM-1, in particular, is expressed on neutrophils and monocytes and is a potent amplifier of inflammatory responses. LPS and other microbial products induce up-regulation of cell surface-localized TREM-1 and the release of its soluble form, sTREM-1. Two hypotheses have been advanced to explain the origin of sTREM-1: alternative splicing of TREM-1 mRNA and proteolytic cleavage(s) of mature, membrane-anchored TREM-1. In this report, we present conclusive evidence in favor of the proteolytic mechanism of sTREM-1 generation. No alternative splicing forms of TREM-1 were detected in monocytes/macrophages. Besides, metalloproteinase inhibitors increased the stability of TREM-1 at the cell surface while significantly reducing sTREM-1 release in cultures of LPS-challenged human monocytes and neutrophils. We conclude that metalloproteinases are responsible for shedding of the TREM-1 ectodomain through proteolytic cleavage of its long juxtamembrane linker.     

Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis

TREM-1 is a recently discovered receptor expressed on neutrophils and macrophages. Blocking of TREM-1 signaling improves the survival of mice with bacterial sepsis. However, the precise mechanism by which TREM-1 modulates the inflammatory responses is poorly defined. In this study, we investigated the role of TREM-1 in Pseudomonas aeruginosa-induced peritonitis. Our results showed that TREM-1 was not expressed on lymphocytes but emerged on the cell surface of neutrophils and peritoneal macrophages. Blockade of TREM-1 signaling significantly prolonged survival of mice with P. aeruginosa-induced peritonitis. However, blocking TREM-1 signaling had no effect on macrophage phagocytosis in vitro. Interestingly, the expression of the costimulatory molecules CD40 and CD86 on macrophages was significantly decreased after blocking TREM-1 signaling. Furthermore, interfering with TREM-1 engagement led to significant reduction of pro-inflammatory mediators such as IL-1, TNF-α, MCP-1 and IFN-γ. Therefore, our results showed that TREM-1 could be a potential therapeutic target for bacterial sepsis.     

The Neutrophil-Lymphocyte Count Ratio in Patients with Community-Acquired Pneumonia

Study Objective

The neutrophil-lymphocyte count ratio (NLCR) has been identified as a predictor of bacteremia in medical emergencies. The aim of this study was to investigate the value of the NLCR in patients with community-acquired pneumonia (CAP).

Methods and Results

Consecutive adult patients were prospectively studied. Pneumonia severity (CURB-65 score), clinical characteristics, complications and outcomes were related to the NLCR and compared with C-reactive protein (CRP), neutrophil count, white blood cell (WBC) count. The study cohort consisted of 395 patients diagnosed with CAP. The mean age of the patients was 63.4±16.0 years. 87.6% (346/395) of the patients required hospital admission, 7.8% (31/395) patients were admitted to the Intensive Care Unit (ICU) and 5.8% (23/395) patients of the study cohort died. The NLCR was increased in all patients, predicted adverse medical outcome and consistently increased as the CURB-65 score advanced. NLCR levels (mean ± SD) were significantly higher in non-survivors (23.3±16.8) than in survivors (13.0±11.4). The receiver-operating characteristic (ROC) curve for NLCR predicting mortality showed an area under the curve (AUC) of 0.701. This was better than the AUC for the neutrophil count, WBC count, lymphocyte count and CRP level (0.681, 0.672, 0.630 and 0.565, respectively).

Conclusion

Admission NLCR at the emergency department predicts severity and outcome of CAP with a higher prognostic accuracy as compared with traditional infection markers.     

Soluble form of suppression of tumorigenicity-2 predicts clinical stability of inpatients with community-acquired pneumonia

The soluble form of the suppression of tumorigenicity-2 (sST2) is a biomarker for risk classification and prognosis of heart failure, and its production and secretion in the alveolar epithelium are significantly correlated with the inflammation-inducing in pulmonary diseases. However, the predictive value of sST2 in pulmonary disease had not been widely studied. This study investigated the potential value in prognosis and risk classification of sST2 in patients with community-acquired pneumonia. Clinical data of ninety-three CAP inpatients were retrieved and their sST2 and other clinical indices were studied. Cox regression models were constructed to probe the sST2’s predictive value for patients’ restoring clinical stability and its additive effect on pneumonia severity index and CURB-65 scores. Patients who did not reach clinical stability within the defined time (30 days from hospitalization) have had significantly higher levels of sST2 at admission (P < 0.05). In univariate and multivariate Cox regression analysis, a high sST2 level (≥72.8 ng/mL) was an independent reverse predictor of clinical stability (P < 0.05). The Cox regression model combined with sST2 and CURB-65 (AUC: 0.96) provided a more accurate risk classification than CURB-65 (AUC:0.89) alone (NRI: 1.18, IDI: 0.16, P < 0.05). The Cox regression model combined with sST2 and pneumonia severity index (AUC: 0.96) also provided a more accurate risk classification than pneumonia severity index (AUC:0.93) alone (NRI: 0.06; IDI: 0.06, P < 0.05). sST2 at admission can be used as an independent early prognostic indicator for CAP patients. Moreover, it can improve the predictive power of CURB-65 and pneumonia severity index score.     

Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer

Raised serum levels of interleukin 6 (IL-6) have been described in cancer patients. This cytokine mediates the acute phase response and has been also involved in the pathogenesis of cancer cachexia. The objectives of the present study were: (1) to determine the relationships of IL-6 and other cytokines with neoplasia extension, acute phase response and nutritional status, in lung cancer patients; and (2) to establish the prognostic value of serum cytokine levels. A prospective study in which IL-1, IL-2, IL-6, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been determined in 66 newly diagnosed lung cancer patients. Nutritional status was assessed objectively. Serum levels of growth hormone (GH), insulin growth factor 1 (IGF-1) and acute phase reactants as C Reactive Protein, alpha1 antitrypsin and ferritine, were determined. Increased IL-6 levels were related to extensive disease, impaired performance status, enhanced acute phase response and malnutrition. Raised serum IL-6 levels, extensive disease, low Karnofsky index, malnutrition, acute phase response and low IFN-gamma were all related to a shorter survival. When assessed by a multivariate analysis, IL-6 kept its independent prognostic value together with age, disease extension, and decreased IFN-gamma serum levels.IL-6 is increased in lung cancer patients, enhances the acute phase response in them, and is correlated with poor nutritional status, impaired performance status and shorter survival.     

Increased sTREM-1 plasma concentrations are associated with poor clinical outcomes in patients with COVID-19

Patients with sepsis display increased concentrations of sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells 1), and a phase II clinical trial focusing on TREM-1 modulation is ongoing. We investigated whether sTREM-1 circulating concentrations are associated with the outcome of patients with coronavirus disease 2019 (COVID-19) to assess the role of this pathway in COVID-19. This observational study was performed in two independent cohorts of patients with COVID-19. Plasma concentrations of sTREM-1 were assessed after ICU admission (pilot cohort) or after COVID-19 diagnosis (validation cohort). Routine laboratory and clinical parameters were collected from electronic patient files. Results showed sTREM-1 plasma concentrations were significantly elevated in patients with COVID-19 (161 [129–196] pg/ml) compared to healthy controls (104 [75–124] pg/ml; P<0.001). Patients with severe COVID-19 needing ICU admission displayed even higher sTREM-1 concentrations compared to less severely ill COVID-19 patients receiving clinical ward-based care (235 [176–319] pg/ml and 195 [139–283] pg/ml, respectively, P = 0.017). In addition, higher sTREM-1 plasma concentrations were observed in patients who did not survive the infection (326 [207–445] pg/ml) compared to survivors (199 [142–278] pg/ml, P<0.001). Survival analyses indicated that patients with higher sTREM-1 concentrations are at higher risk for death (hazard ratio = 3.3, 95%CI: 1.4–7.8). In conclusion, plasma sTREM-1 concentrations are elevated in patients with COVID-19, relate to disease severity, and discriminate between survivors and non-survivors. This suggests that the TREM-1 pathway is involved in the inflammatory reaction and the disease course of COVID-19, and therefore may be considered as a therapeutic target in severely ill patients with COVID-19.     

sTREM-1、PCT在社区获得性肺炎早期诊断中的价值

目的:探讨可溶性髓系细胞触发受体-1(soluble triggeringreceptorexpressed on myeloidcells-1,sTREM-1)、降钙素原(procalcitonin,PCT)在社区获得性肺炎(community-acquired pneumonia,CAP)早期诊断中的价值。方法:选择48例CAP住院患者(其中重症肺炎8例)和病毒性上呼吸道感染患者20例,所有病例均在入院后24小时内取血清,采用酶联免疫测定法(ELISA法)测定其血清sTREM-1、PCT水平,并应用受试者工作特征曲线(receiver operating characteristic curve,ROC曲线)分析二者对CAP的诊断价值。结果:入院后24小时内,普通肺炎患者、重症肺炎患者血清sTREM-1、PCT水平均明显高于对照组,且重症肺炎组明显高于普通肺炎组,差异均具有统计学意义(P0.01)。二者诊断CAP的ROC曲线下面积分别为0.884、0.788,联合二者诊断CAP的ROC曲线下面积为0.921。结论:sTREM-1、PCT均可作为CAP早期诊断有价值的参考标志物,sTREM-1比PCT更有参考价值,联合检测血清sTREM-1、PCT水平对CAP的早期诊断价值高于单一指标。     

Soluble TREM-1 as a diagnostic and prognostic biomarker in patients with septic shock: an observational clinical study

Objectives: The impact of TREM-1-mediated inflammation was investigated in different inflammatory settings.

Methods: Secondary analyses of an observational clinical pilot study, including 60 patients with septic shock, 30 postoperative controls and 30 healthy volunteers.

Results: Plasma levels of sTREM-1 were found to identify patients with septic shock more effectively than procalcitonin and C-reactive protein. Moreover, sTREM-1 was identified to be an early predictor for survival in patients with septic shock.

Conclusion: Due to its diagnostic as well as prognostic value in sepsis syndrome, implementation of sTREM-1 measurements in routine diagnostics should be taken into account.     

不同病情老年社区获得性肺炎患者血清ALB、NT-proBNP、PTX3、SDC4的变化及对预后的影响分析

摘要 目的：分析不同病情老年社区获得性肺炎（CAP）患者血清白蛋白（ALB）、N末端脑钠肽前体（NT-proBNP）、正五聚蛋白3（PTX3）、多配体蛋白聚糖4（SDC4）的变化并探讨其对患者预后的影响。方法：选取2019年1月～2020年1月西南医科大学附属医院收治的196例老年CAP患者,根据病情严重程度分为重症CAP组80例和非重症CAP组116例,根据入院后28 d存活情况分为死亡组25例和存活组171例。收集患者临床资料,检测血清ALB、NT-proBNP、PTX3、SDC4水平。通过多因素Logistic回归分析老年CAP患者死亡的影响因素,受试者工作特征（ROC）曲线分析血清ALB、NT-proBNP、PTX3、SDC4水平对老年CAP患者死亡风险的预测价值。结果：与非重症CAP组比较,重症CAP组血清ALB、SDC4水平降低,NT-proBNP、PTX3水平升高（P＜0.05）。多因素Logistic回归分析显示,ALB升高、SDC4升高为老年CAP患者死亡的保护因素,呼吸频率加快、CURB-65评分增加、肺炎严重指数（PSI）增加、NT-proBNP升高、PTX3升高为老年CAP患者死亡的危险因素（P＜0.05）。ROC曲线分析显示,血清ALB、NT-proBNP、PTX3、SDC4水平联合预测老年CAP患者死亡的曲线下面积（AUC）大于各指标单独预测。结论：老年CAP患者体内血清ALB、SDC4水平降低,NT-proBNP、PTX3水平升高,血清ALB、NT-proBNP、PTX3、SDC4与患者病情加重和预后有关,具有作为老年CAP患者预后评估指标的潜能。     

Insulin-like growth factor-1 (IGF-1) and growth hormone (GH) in immunity and inflammation

In recent years many efforts have been undertaken to elucidate the complex interactions between mediators of the endocrine system and the immune system. The main effector of growth hormone (GH) is insulin-like growth factor-1 (IGF-1), an endocrine mediator of growth and development under physiological conditions. Besides this important function, IGF-1 also plays a prominent role in the regulation of immunity and inflammation. This article will address the involvement of IGF-1 in innate as well as acquired immunity and host-defense. We also discuss the role of IGF-1 in the course of inflammatory disorders, including sepsis and sepsis-induced catabolism as well as degenerative arthritis. Based on recent insights, we finally examine the pathophysiological background, potential pitfalls and perspectives of IGF-1 suppletion therapy in these conditions.     

Inhibition of TREM-1 and Dectin-1 Alleviates the Severity of Fungal Keratitis by Modulating Innate Immune Responses

Purpose

To explore the possibility that inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) and Dendritic cell-associated C-type lectin-1(Dectin-1) could modulate the innate immune response and alleviate the severity of corneal fungal keratitis.

Method

TREM-1 and Dectin-1 expression was detected in fungus-infected human corneal specimens by real-time PCR. C57BL/6 (B6) mice were injected with Aspergillus fumigatus and divided into 4 groups that received subconjunctival injections of PBS and IgG as a control (group I), mTREM-1/IgG fusion protein (group II), the soluble β-glucan antagonist laminarin (group III), or mTREM-1/Fc and laminarin (group IV). Corneal virulence was evaluated based on clinical scores. TREM-1 and Dectin-1 mRNA levels were assayed using real-time PCR. The distribution patterns of TREM-1, Dectin-1 and cellular infiltrates in fungus-infected corneas were examined by immunohistochemistry. Moreover, changes in T Helper Type1 (Th1)-/ T Helper Type1 (Th2)- type cytokines and proinflammatory cytokines were measured.

Results

The expression of TREM-1 and Dectin-1 increased significantly and correlated positively with the progression of fungal keratitis. Most infiltrated cells were neutrophils and secondarily macrophages in infected cornea. The clinical scores decreased after interfering with TREM-1 and Dectin-1 expression in infected mouse corneas. Levels of Th1-type cytokines including interleukin-12 (IL-12), IL-18 and interferon-γ (IFN-γ) were decreased in the cornea, while the levels of Th2-type cytokines, including IL-4, IL-5 and IL-10, showed obvious increases.

Conclusion

TREM-1 and Dectin-1 function concurrently in the corneal innate immune response by regulating inflammatory cytokine expression in fungal keratitis. Inhibition of TREM-1 and Dectin-1 can alleviate the severity of corneal damage by downregulating the excessive inflammatory response.     

Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1beta and IL-1ra production in multiple sclerosis

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disorder, with a considerable genetic influence on susceptibility and disease course. Cytokines play an important role in MS pathophysiology, and genes encoding various cytokines are logical candidates to assess possible associations with MS susceptibility and disease course. We previously reported an association of a combination of polymorphisms in the interleukin (IL)-1B and IL-1 receptor antagonist (IL-1RN) genes (i.e. IL-1RN allele 2+/IL-1B(+3959)allele 2-) with disease severity in MS. Extending this observation, we investigated whether IL-1beta and IL-1ra production differed depending on carriership of this gene combination. METHODS: Twenty MS patients and 20 controls were selected based upon carriership of the specific combination. In whole blood, in vitro IL-1beta and IL-1ra production was determined by enzyme-linked immunosorbent-assay after 6 and 24 h of stimulation with lipopolysaccharide. RESULTS: Carriers of the specific combination produced more IL-1ra, especially in MS patients, although not significantly. IL-1ra production was significantly higher in individuals homozygous for IL-1RN allele 2. In patients, Il-1ra production was higher and IL-1beta production lower compared with controls. In primary progressive patients, the IL-1beta /IL-1ra ratio was significantly lower than in relapsing-remitting patients. CONCLUSION: Our results suggest higher in vitro IL-1ra production in carriers of IL-1RN allele 2, with an indication of an allelic dose-effect relationship.