Interleukin-6 significantly improves predictive value of systemic inflammatory response syndrome for predicting severe acute pancreatitis

Background

Predicting severe acute pancreatitis (AP) is important for triage, prognosis, and designing therapeutic trials. Persistent systemic inflammatory response syndrome (SIRS) predicts severe AP but its diagnostic accuracy is suboptimal. Our objective was to study if cytokine levels could improve the predictive value of clinical variables for the development of severe AP.

Ghrelin inhibits IKKβ/NF-κB activation and reduces pro-inflammatory cytokine production in pancreatic acinar AR42J cells treated with cerulein

Background: Previous studies have provided conflicting results regarding whether the serum ghrelin concentration can reflect the severity of acute pancreatitis(AP). The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether altered ghrelin expression in pancreatic acinar cells influences IKK β/NF-κ B signaling and pro-inflammatory cytokine production. Methods: Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate, respectively. After successful model induction, serum ghrelin, tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) concentrations were determined by enzyme-linked immunosorbent assay, and IKK β/NF-κ B activation was assessed by immunohistochemistry. Subsequently, stable overexpression or knockdown of ghrelin in AR42 J cells was achieved by lentiviral transfection. After transfected cells and control cells were treated with cerulein for 24 h, the TNF-αand IL-1 β levels in the supernatants were determined by enzyme-linked immunosorbent assay, and the expression levels of p-p65, IKK β, and p-IKK β were detected by Western blotting. Results: In rat AP models, AP severity was correlated with increased IKK β/NF-κ B activation, proinflammatory cytokine production, and ghrelin secretion. The levels of pro-inflammatory cytokines TNF-αand IL-1 β as well as IKK β/NF-κ B signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression. Conclusions: Serum ghrelin is related to the severity of AP. Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKK β/NF-κ B signaling pathway.     

Serum soluble suppression of tumorigenicity 2 as a novel inflammatory marker predicts the severity of acute pancreatitis

BACKGROUNDAcute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses.AIMTo investigate the role of sST2 in AP.METHODSWe assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria. RESULTSSerum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001–1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003–1.009), P = 0.000, OR: 1.002 (1.001–1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups. CONCLUSIONsST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.     

High plasma levels of the pro-inflammatory cytokine IL-22 and the anti-inflammatory cytokines IL-10 and IL-1ra in acute pancreatitis

Background/objectivesPancreatic acinar cells are major targets of IL-22. Our aim is to study early plasma levels of IL-22, of pro- and anti-inflammatory cytokines in acute pancreatitis, and their association with severity or necrosis infection.MethodsConsecutive patients admitted to the Department of Hepato-Gastroenterology at Poitiers University of Medicine Hospital (France) with a diagnosis of AP were prospectively enrolled. Plasma concentrations of IL-22, IL-6, IL-8, IL-1 α, IL-1β, TNF- α, IFN-γ, IL-17A, IL-10, IL-1ra and IL-4 were assessed by multiple immunoassay at the admission time. A thoracoabdominal contrast-enhanced CT scan was performed at day 2.ResultsSixty-two patients were included; 13 patients (21%) had a severe acute pancreatitis, 5 patients (8%) developed necrosis infection and 29 patients (47%) had pleural effusion. Plasma levels of IL-22 were high in AP (135 ± 31 vs 4.2 ± 1.8 pg/ml for controls, p < 0.05), but did not correlate with the severity of the disease, whereas IL-6, IL-10 and IL-1ra where enhanced in patients with severe acute pancreatitis and with pleural effusion. Patients who further developed necrosis infection had higher levels of IL-1ra at admission (p = 0.0004).ConclusionIn acute pancreatitis, high plasma levels of IL-22 are observed, regardless the severity of the disease. In contrast, severe forms were associated with increased levels of IL-6, IL-10 and IL-1ra. The beneficial or deleterious role of IL-22 in AP remains to be further studied.     

Elevated level of interleukin-6 predicts organ failure and severe disease in patients with acute pancreatitis

BACKGROUND AND AIM: Cytokines play an important role in the pathogenesis of acute pancreatitis (AP). The aim of the present paper was to study the profile of anti- and proinflammatory cytokines in AP and to determine their predictive value for severity of AP, organ failure and mortality. METHODS: Consecutive patients with AP were included in the study. Cytokines were measured in those patients who presented within the first 72 h of the onset of AP. Plasma levels of proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-Ibeta, IL-6 and anti-inflammatory cytokine IL-10 were measured on days 1, 3, 7 and 14 of AP. RESULTS: Of 108 patients, 30 presented within 72 h of the onset (mean age 40.27 +/- 13.89 years; 22 males). Of the 30 patients, 13 (43.3%) had severe and 17 (56.7%) had mild pancreatitis. Eleven (36.7%) patients developed organ failure and three died. The level of IL-6 on day 3 was significantly higher in severe pancreatitis than in mild pancreatitis (146.29 +/- 57.53 pg/mL vs 91.42 +/- 71.65 pg/mL; P = 0.04) and was significantly higher in patients who developed organ failure compared with those who did not (161.59 +/- 53.46 pg/mL vs 88.16 +/- 65.50 pg/mL; P = 0.004). At a cut-off value of 122 pg/mL on day 3, IL-6 predicted organ failure and severe pancreatitis with a sensitivity and specificity of 81.8% and 77.7%, respectively. TNF-alpha and IL-10 were detectable only in one-third of patients and were not related to the severity of pancreatitis, while Il-1beta was not detectable. CONCLUSION: Elevated levels of IL-6 predicted organ failure and severe pancreatitis and suggested its pathophysiological significance in AP.     

Obesity and Fat Distribution Imply a Greater Systemic Inflammatory Response and a Worse Prognosis in Acute Pancreatitis

Background and Aims: Acute pancreatitis (AP) is a systemic inflammatory disease. It is already known that obesity and central fat distribution are related to the severity of AP, but the intimate mechanism of this relationship remains unknown. Obesity and central fat distribution are associated with an inflammatory state that could amplify the systemic inflammatory response (SIR) in AP. The aim of this study was to investigate how obesity and body fat distribution correlate with the SIR and severity of AP. Methods: 85 consecutive patients with AP were studied. Body mass index, body fat distribution and previous comorbidity were obtained at admission. The SIR was assessed by the serum levels of interleukin (IL)-Iβ, IL-1ra, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor-α (TNF-α) and C-reactive protein. Serum concentrations of the previously mentioned cytokines were also determined in a control group of 40 healthy volunteers. Results: 63 patients (74%) had mild AP and 22 patients (26%) had severe AP. All the cytokines except IL-12p70 and TNF-α were increased in the AP group in comparison with the control group. The SIR was significantly increased in patients with severe AP. Obese patients and patients with central fat distribution had significantly more comorbidity, a higher proportion of severe AP and more intense SIR. Patients with comorbidity had a significantly higher proportion of severe AP and more SIR. Conclusion: The severity of AP in obese patients and in patients with central fat distribution seems to be related to the comorbidity and the amplification of SIR.     

The Effect of Intestinal Permeability and Endotoxemia on the Prognosis of Acute Pancreatitis

Background/Aims

Early intestinal mucosal damage plays an important role in severe acute pancreatitis (AP). Previous studies have shown that intestinal permeability (IP), serum endotoxin and cytokines contribute to the early intestinal barrier dysfunction in AP. This study explored the predictive capacity of IP, endotoxemia and cytokines as prognostic indicators in AP patients.

Methods

Eighty-seven AP patients were included in the study. The patients were classified into three groups according to the Balthazar computed tomography severity index (CTSI). We compared the biochemical parameters, including IP, serum endotoxin level and cytokine level among the three groups. The associations of IP with serum endotoxin, cytokines, CTSI, and other widely used biochemical parameters and scoring systems were also examined.

Results

IP, serum endotoxin, interleukin (IL-6) and tumor necrosis factor (TNF)-α had a positive correlation with the CTSI of AP. Endotoxin, IL-6, TNF-α, CTSI, the Ranson/APACHE II score, the duration of hospital stay, complications and death significantly affect IP in the AP patients.

Conclusions

We believe that IP with subsidiary measurements of serum endotoxin, IL-6 and TNF-α may be reliable markers for predicting the prognosis of AP. Further studies that can restore and preserve gut barrier function in AP patients are warranted.     

Predicting severe acute pancreatitis in children based on serum lipase and calcium: A multicentre retrospective cohort study

ObjectiveThis study aims to identify predictors of severe paediatric AP based on laboratory trends and peak/trough values on day 2 (D2) after presentation. The performance of identified predictors was first assessed and then combined with the previously validated sensitive predictor serum lipase ≥7 times the upper limit of normal (× ULN) on day 1 (D1).MethodsA retrospective review of children with AP (January 2000–July 2011) was performed at three tertiary referral hospitals (two in Australia, one in the Netherlands). Trends of candidate predictors were analysed using the percentage change from D1 to D2 or peak/trough values within 48 h after presentation.Results175 AP episodes (including 50 severe episodes [29%]) were identified. Serum lipase ≥50% decrease on D2 (sensitivity 73%, specificity 54%) and calcium trough ≤2.15 mmol/L within 48 h (sensitivity 59%, specificity 81%) were identified as statistically significant predictors for severe AP. By combining the newly identified predictors with the previously validated predictor serum lipase ≥7× ULN on D1 (sensitivity 82%, specificity 53%), specificity improved to predict severe AP on D2 with the addition of: (i) serum lipase ≥50% decrease (sensitivity 67%, specificity 79%), or (ii) trough calcium ≤2.15 mmol/L (sensitivity 46%, specificity 89%).ConclusionsSerum lipase and calcium, may be helpful in predicting severity of paediatric AP. There may be a clinical role on D1 for using serum lipase ≥7× ULN (high sensitivity), and on D2 for combining D1 serum lipase ≥7× ULN with calcium trough ≤2.15 mmol/L within 48 h (high specificity) to help predict severe paediatric AP.     

Effects of curcumin on proinflammatory cytokines and tissue injury in the early and late phases of experimental acute pancreatitis

Background & aimsAcute pancreatitis (AP) varies from mild to severe necrotizing changes with high mortality. The objective of the current study was to investigate the effects of curcumin on tissue injury and proinflammatory cytokines in the early and late phases of AP.MethodsAP was induced by sodium taurocholate in rats (n = 140). First group was left untreated. Group II received 100 mg/kg curcumin daily starting 20 days before AP induction. The rats were allocated into 7 sub-groups (n:5) and were sacrificed at 2, 6, 12, 24, 72, 144 and 288 h following the induction of AP. Blood and pancreatic tissue samples were collected for biochemical and histopathologic evaluations and the assessment of protein and mRNA levels, as well.ResultsCurcumin decreased total histopathologic scores in comparison with those of the taurocholate group (P < 0.05). Curcumin increased Caspase-3 activity and decreased trypsin activity, while inhibited nuclear factor-κ (NF-κB) at all time points (P < 0.05) and moreover reduced activator protein-1 (AP-1). Curcumin decreased chemokine (except for 288 h), TNF-α (except for 2 and 24 h), IL-6 (except for 2, 6 and 288 h) and iNOS (except for 144 and 288 h) mRNA levels (P < 0.05). Curcumin serum nitric oxide (NO) (except for 144 and 288 h) levels were reduced, as well.ConclusionsIn conclusion, curcumin reduced tissue injury, trypsin activation and inhibited NF-κB and AP-1. However TNF-α, IL-6 and iNOS and NO were not inhibited at all time points. Therefore no direct correlation was detected in the subgroups between tissue injury, proinflammatory cytokines and oxidative enzymes.     

Neopterin in Acute Pancreatitis

Background: Activation of the cellular immune system may play a role in the pathogenesis of acute pancreatitis (AP); it has recently been proposed that excessive leukocyte stimulation may lead to the most severe forms of AP. The aim of this study was to investigate serum neopterin, a useful in vivo marker of macrophage activation, in mild and severe AP and its relationship with other markers of leukocyte activation, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Methods: Serum levels of neopterin (mmol/ml), IL-6 (pg/ml), and TNF (pg/ml) were measured on the 1st and 7th day of hospitalization in 17 patients with severe AP and 24 with mild AP. Severe AP was defined in accordance with the Atlanta criteria: all patients have necrosis at contrast-enhanced computerized tomography scan. Results: Day 1: Neopterin and IL-6 levels were significantly higher in the severe than in the mild AP and normal controls; mild AP values were also significantly higher than in normal controls. The best neopterin cutoff level we obtained (30 mmol/ml) reached a specificity of 76% and a sensitivity of 46% in distinguishing severe from mild AP. Day 7: Neopterin was significantly higher in severe AP than in mild AP and in normal controls; no difference was seen between mild AP values and normal controls; neopterin serum levels were significantly higher on day 7 than on day 1 in severe AP but not in mild AP; in both groups of patients IL-6 was significantly higher on day 1 than on day 7. Using a neopterin cutoff level of 40 mmol/ml, we found a specificity and sensitivity value of 92% in differentiating severe from mild AP. With regard to TNF values, no difference was seen on days 1 and 7 in the two groups of patients in comparison with normal controls. Neopterin serum values did not correlate with IL-6 and TNF on either day. Conclusions: These results confirm the activation of the cellular immune system in AP. Initially enhanced NEOP and IL-6 serum levels reflect the severity of the disease; neopterin may be considered a reliable prognostic indicator also at a distance from AP onset because its levels increase during the 1st week of AP in patients with severe forms only.     

Hypertriglyceridaemia-associated acute pancreatitis: diagnosis and impact on severity

BackgroundThe level of hypertriglyceridaemia (HTG) at which the risk of acute pancreatitis (AP) increases and the impact of HTG on AP attributable to other aetiologies remains unclear.MethodsWe compared clinical outcomes of patients admitted within 48 h of the onset of abdominal pain from a first episode of AP and admission serum triglyceride levels of either <5.65 mmol/l (<500 mg/dl) or ≥5.65 to <11.3 mmol/l (moderate HTG) or ≥11.3 mmol/l (≥1000 mg/dl, severe HTG).ResultsAmong a cohort of 1,233 patients with AP there were significant progressive increases in all major deleterious clinical outcomes including mortality (all P_trend < 0.05) that were directly dependent on admission triglyceride levels. Outcomes were improved by earlier presentation (<24 h compared to 24–48 h from abdominal pain onset). Patients with severe HTG and a concomitant aetiology (n = 68) had significantly more persistent organ failure, pancreatic necrosis and longer hospital stays (P < 0.05) than those with severe HTG alone (n = 206).ConclusionsThere appears to be an association between HTG grade and the severity of AP. Severe HTG significantly increased the severity of AP, over AP attributable to other aetiologies. Moderate as well as severe HTG can be used as a criterion for the diagnosis of HTG-associated AP.     

Amalgamation of systemic inflammatory response syndrome score with C-reactive protein level in evaluating acute pancreatitis severity in children

Background and aim: Systemic inflammatory response syndrome (SIRS) has to do with how the body reacts to injury. Herein, we analyzed the clinical features of acute pancreatitis (AP) in children with SIRS complication and investigated the role of SIRS score combined with C-reactive protein (CRP) level in assessing AP severity in children.

Methods: This retrospective cohort study involved 111 children hospitalized with AP at the Children's Hospital of Zhejiang University School of Medicine between January 2012 and August 2017. Presence of SIRS, demographic data, clinical information and laboratory test results on admission were statistically examined.

Results: Out of the 111 AP cases, 45 were diagnosed with SIRS. Differences in CRP, interleukin-6 (IL-6), age, temperature, heart rate (HR), white blood cell (WBC), neutrophil count (NC), body mass index (BMI), duration of onset of disease symptoms as well as cases requiring intensive care unit (ICU) treatment were significantly higher in patients with SIRS than those without SIRS (p?p?p?=?.02) and fever (OR?=?3.56, p?=?.007). SIRS was an independent predictor for AP severity (OR?=?10.820, p?=?.005). The optimal cut-off value of CRP was 27.5?mg/L for severe AP classification according to receiver operating characteristic (ROC) (area under curve was 0.733).

Conclusion: Amalgamation of SIRS criterion with CRP level potentially plays an important role in assessing AP severity in children.     

Early inflammatory response in acute pancreatitis is little affected by body mass index

Objective. Obesity is a known risk factor for severe acute pancreatitis (AP), but the mechanism by which it affects the severity of AP is not fully understood. The main objective of this study was to investigate the relationship between obesity and inflammatory markers in AP. Material and methods. Thirty patients with AP who developed organ failure (Group I) and 87 patients with AP who survived without organ failure (Group II) were studied. Patients’ height and weight were measured at admission for calculation of body mass index (BMI). Blood samples were taken at admission for measurement of plasma interleukin (IL)-1β, IL-6, IL-10, IL-1 receptor antagonist, procalcitonin, C-reactive protein (CRP) and monocyte human leucocyte antigen (HLA)-DR expression. Results. Group I patients had higher BMI values (median 26.2 kg/m²) than Group II patients (25.2 kg/m²), p=0.033. Both CRP values and monocyte HLA-DR expression showed a significant correlation with BMI (Spearman's rank correlation r=0.32, p=0.003 and r=?0.33, p=0.002, respectively). The correlation between BMI and monocyte HLA-DR expression was significant in Group II patients (r=?0.34, p=0.002) but not in Group I patients (r=?0.02, p>0.05). There was no correlation between BMI and IL-1β, IL-6, IL-10, IL-1 receptor antagonist or procalcitonin. Conclusions. BMI did not affect either pro-inflammatory or anti-inflammatory cytokine levels in early AP. However, in patients with mild AP, BMI correlated positively with CRP levels and inversely with monocyte HLA-DR expression, which might reflect an amplified inflammatory response in these patients. Taken together, acute inflammatory response in AP, which ultimately determines the severity of AP, was little affected by BMI.     

Prediction of severe acute pancreatitis：Current knowledge and novel insights

Acute pancreatitis （AP） is a common and potentially lethal acute inflammatory process with a highly variable clinical course. It is still unclear why some patients progress to organ failure and others do not. Physicians, ability to predict which patients will develop severe disease is limited. Routine clinical and laboratory data and multi-factorial clinical scores measured on admission and during the first 48 h of hospitalization are currently the standards of care used to estimate the magnitude of the inflammatory response to injury. Current literature highlights several common environmental, metabolic and genetic factors that increase the risk of AP development and subsequent adverse sequelae. Several cytokines have been found to play a critical role in the pathogenesis of AP by driving the subsequent inflammatory response, to include tumor necrosis factor-α （TNF-α）, Interleukin-1 （IL-1）, IL-6 and monocyte chemotactic protein-1 （MCP-1）. Large, prospective studies are still needed to address these questions by identifying AP risk factors and serum biomarkers of severe disease.     

炎症因子联合Ranson评分预测急性胰腺炎严重程度和指导临床治疗的价值分析

目的 探讨炎症因子联合Ranson评分预测急性胰腺炎（AP）严重程度和指导临床治疗的价值。方法 根据2012年Atlanta标准将150例AP患者分为轻度组（50例）、中度组（50例）和重度组（50例），比较各组血清炎症因子[白细胞介素（IL）-6、降钙素原（PCT）、C反应蛋白（CRP）、IL-8、IL-10]水平和Ranson评分，并统计各组病死率，绘制受试者工作特征（ROC）曲线，计算曲线下面积（AUC），比较各指标评估器官功能衰竭和病死率的价值。结果 3组患者发病12h、24h、48h时的PCT、IL-6、CRP逐渐升高，且随着病情严重程度增加而逐渐增高（P＜0.05）；3组患者发病24h时的IL-10水平高于发病12h，但发病48h低于发病24h（P＜0.05）；轻、中、重度组Ranson评分随病情严重程度增加呈递增趋势（P＜0.05）；重度组病死率（16.0%）高于轻度组（0）和中度组（2.0%，P＜0.05）。血清炎症因子中，IL-6评估器官功能衰竭和病死率的AUC＞PCT、CRP；CRP评估胰腺坏死的AUC＞PCT、IL-6；Ranson评分评估器官功能衰竭和病死率的AUC＞PCT、IL-6、CRP；PCT+IL-6+CRP+Ranson评分评估器官功能衰竭、胰腺坏死及病死率AUC均＞Ranson评分及任一血清炎症因子。结论IL-6评估AP患者器官功能衰竭、病死率价值较高，CRP评估胰腺坏死价值较高，PCT、IL-6、CRP与Ranson评分系统联合应用可进一步提高对其器官功能衰竭、胰腺坏死、病死率的预测能力，为临床治疗策略的选择提供参考。     

Correlation of peripheral Th17 cells and Th17-associated cytokines to the severity of carotid artery plaque and its clinical implication

ObjectiveAtherosclerosis is a chronic inflammatory disease regulated by T lymphocyte subsets. Th17 cells reportedly play important roles in the development of inflammatory and autoimmune diseases. In this study, we investigated the contributions of circulating Th17 cells and plasma Th17-associated cytokines to carotid artery plaques.MethodsBased on carotid artery ultrasonography, 280 atherosclerosis patients were categorized both by: (1) 4 levels for extent and severity of plaques (Level 1 = least severe; Level 4 = most severe) and (2) 5 groups for ultrasound features of carotid artery plaques (none, flat, soft, hard, ulcerated). Peripheral blood Th17 cell frequencies and plasma concentrations of Th17-associated cytokines (IL-17, IL-6, and TNF-α) were also determined.ResultsFor groups categorized by the extent and severity of carotid artery plaques, Th17 cell frequencies, common carotid artery intima-media thickness (CCA-IMT), and Crouse scores were significantly increased in higher level groups (Levels 3 and 4) than in lower level groups (Levels 1 and 2), and plasma concentrations of IL-17, IL-6, and TNF-α increased with increased levels of plaque severity. The same pattern was found for groups categorized by ultrasound features of carotid artery plaques. The results of Pearson correlation and multiple linear regression analyses showed that both CCA-IMT and Crouse scores for carotid artery plaques were significantly and positively correlated with Th17 cell frequencies and plasma Th17-associated cytokine concentrations.ConclusionThese results suggest that increased frequencies of circulating Th17 cells and Th17-associated cytokines are correlated to the severity and progression of carotid artery plaques.     

The predictive value of epicardial fat volume for clinical severity of COVID-19

IntroductionEpicardial adipose tissue serves as a source of inflammatory cytokines and mediators. Cytokine storm is an important cause of morbidity and mortality in coronavirus disease 2019 (COVID-19).ObjectivesTo investigate the association between epicardial fat volume (EFV), inflammatory biomarkers and clinical severity of COVID-19.MethodsThis retrospective study included 101 patients who were infected with COVID-19. Serum inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and ferritin levels were measured. Computed tomography images were analyzed and semi-automated measurements for EFV were obtained. The primary composite endpoint was admission to the intensive care unit (ICU) or death.ResultsThe primary composite endpoint occurred in 25.1% (n=26) of patients (mean age 64.8±14.8 years, 14 male). A total of 10 patients died. EFV, CRP, PCT, ferritin and IL-6 levels were significantly higher in ICU patients. Moreover, a positive correlation was determined between EFV and CRP (r: 0.494, p<0.001), PCT (r: 0.287, p=0.005), ferritin (r: 0.265, p=0.01) and IL-6 (r: 0.311, p=0.005). On receiver operating characteristic analysis, patients with EFV >102 cm³ were more likely to have severe complications. In multivariate logistic regression analysis, EFV independently predicted admission to the ICU at a significant level (OR: 1.02, 95% CI: 1.01-1.03, p=0.025).ConclusionEFV and serum CRP, IL-6, PCT and ferritin levels can effectively assess disease severity and predict the outcome in patients with COVID-19. EFV is an independent predictor of admission to the ICU in hospitalized COVID-19 patients.     

Anti-hypertensive and renoprotective effects of berberine in spontaneously hypertensive rats

Abstract

Objectives: We aimed to investigate the effects of berberine on renin–angiotensin system (RAS) and pro-inflammatory cytokines, as well as its effects on blood pressure and renal damage in spontaneously hypertensive rats. Methods: Berberine was administrated to spontaneously hypertensive rats (SHR rats) between 3 and 20 weeks of age. Blood pressure was monitored in 3-, 6-, 9-, 12-, 16- and 20-week-old SHR rats and age-matched Wistar Kyoto rats (WKY rats). Besides, we measured levels of angiotensin II, aldosterone and pre-inflammatory cytokines (IL-6, IL-17, IL-23) in serum and kidney, as well as levels of collagen III and collagen IV in kidney and urinary markers of renal injury (osteopontin, kidney-injury-molecule (KIM-1) and albumin) in 3-, 6-, 9-, 12-, 16- and 20-week-old SHR rats and WKY rats. Glomerulosclerosis was also assessed with hematoxylin and eosin staining. Results: SHR rats developed hypertension at the age of 6 weeks and had increased levels of angiotensin II, aldosterone, IL-6, IL-17, IL-23, collagen III, collagen IV, osteopontin, KIM-1 and albumin, as well as more severe glomerulosclerosis, compared to the aged-matched WKY rats. Berberine delayed the onset and attenuated the severity of hypertension, as well as partially inhibited the increases of the above substances in SHR rats. Conclusion: Berberine could delay the onset and attenuate the severity of hypertension, as well as ameliorate hypertension-induced renal damage in SHR rats. Furthermore, berberine could inhibit the activities of RAS and pre-inflammatory cytokines IL-6, IL-17 and IL-23, which are involved in the pathophysiology of hypertension.     

Role of nuclear factor-κB,reactive oxygen species and cellular signaling in the early phase of acute pancreatitis

Objective Increased knowledge of regulation of signaling proteins in acute pancreatitis (AP) could potentially contribute to the development of novel agents targeted at regulation of cellular signaling. Material and methods Severe AP was induced by administration of 5% sodium taurodeoxycholate in rats. Thirty minutes prior to induction of AP, the animals had an intraperitoneal injection of the antioxidant, N-acetylcysteine (NAC; 10 mg/kg), the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC; 100 mg/kg), the ERK inhibitor, PD-98059 (1 mg/kg), or the tyrosine kinase inhibitor, Genistein (1 mg/kg). Plasma levels of IL-6 and IL-10 were determined by ELISA and myeloperoxidase (MPO) levels were measured in the pancreas and lungs 3 and 6 h after sham operation or induction of AP. Results AP results in significant increases in plasma levels of IL-6 at 6 h and IL-10 at 3 and 6 h. Plasma levels of IL-6 were significantly decreased after administration of NAC. NAC pretreatment also increased the ratio of IL-10/IL-6. MPO levels in the pancreas (at 3 and 6 h) and lungs (3 h) were significantly increased in animals with pancreatitis. Pretreatment with NAC, PDTC, PD98059 or Genistein significantly decreased MPO levels in the pancreas at 3 and 6 h and following the administration of PD-98059 or NAC at 6 h. Pretreatment with NAC significantly decreased MPO levels in the lungs at 3 h. Conclusions Pretreatment with NAC could regulate the pro-and anti-inflammatory cytokine balance, probably through NF-κB and ROS signaling pathways. The regulation of signaling pathways during the sequestration of neutrophils in acute pancreatitis seems to vary between organs.