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.     

Is leptin related to systemic inflammatory response in acute pancreatitis？

AIM: To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis. METHODS: Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-α, IL-6, -8 and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria. RESULTS: Fifty-two (29 females) patients were studied. Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6. Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058). CONCLUSION: High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.     

Serum profiles of interleukin-6, interleukin-8, and interleukin-10 in patients with severe and mild acute pancreatitis

Excessive leukocyte activation has been proposed as a key mechanism in the onset of acute pancreatitis. In this study, we assessed the systemic release of various inflammatory mediators and tried to identify differences between patients with mild and severe disease. In a prospective study, 19 patients admitted for severe acute pancreatitis were compared with 24 patients with mild pancreatitis. Serum levels of interleukin-6 (IL-6), IL-8, and IL-10 were determined at the time of admission, and on days 1, 2, and 5 after hospitalization. Severity of pancreatitis was determined according to the Atlanta criteria. IL-6 levels peaked on admission in both groups with significant differences (p < 0.05) from days 0-2. IL-8 levels increased from day 0 in severe cases, and from day 1 in mild cases, to reach a plateau between days 2 and 5; significant differences were observed on days 0 and 1. IL-10 was highest on day 0; it decreased rapidly in mild cases but stayed significantly higher from days 1 to 5 in severe cases. These findings provide new evidence on the role of mediators of the inflammatory/antiinflammatory balance in acute pancreatitis. These molecules appear to be valuable early markers of severity.     

急性呼吸窘迫综合征患者血浆白细胞介素4等含量变化的研究

目的　观察急性呼吸窘迫综合征 (ARDS)患者血浆白细胞介素 4(IL 4)、IL 10和IL 13含量的变化 ,探讨在ARDS发病机制中抗炎机制变化的意义。方法　采用酶联免疫吸附试验 (ELISA)方法 ,检测 2 2例ARDS患者 (ARDS组 )、8例全身炎症反应综合征 (SIRS)患者 (SIRS组 )和 10名健康志愿者 (正常对照组 )的动脉血血浆IL 4、IL 10和IL 13的含量。结果　ARDS组患者的血浆IL 4、IL 10和IL 13含量分别为 (2 61± 5 5 ) μg/L、(45 8± 112 ) μg/L、(5 2 1± 2 0 2 ) μg/L ,SIRS组分别为 (15 5± 2 6)μg/L、(2 60± 5 4) μg/L、(1 69± 0 3 9) μg/L ,正常对照组分别为 (43± 13 ) μg/L、(13 5± 15 ) μg/L、(0 3 3±0 10 ) μg/L ,三组间比较差异具有非常显著性 (P均 <0 0 1) ;SIRS组与正常对照组比较 ,差异也有显著性 (P <0 0 1)。结论　抗炎性细胞因子IL 4、IL 10和IL 13的释放异常 ,可能是ARDS和SIRS的重要发病机制之一。     

A case of severe acute pancreatitis treated with CTR-001 direct hemoperfusion for cytokine apheresis

Severe acute pancreatitis is a clinical entity that can develop into multiple organ failure (MOF), and still has a poor prognosis. It is generally agreed that excessive humoral mediators such as pro-inflammatory cytokines play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP). Furthermore, it has been reported that continuous hemodiafiltration (CHDF) can remove the excess humoral mediators during the hypercytokinemic state of systemic inflammatory response syndrome (SIRS). We experienced a case of severe acute pancreatitis induced by alcohol abuse, on whom we performed cytokine apheresis. The patient was a 46 year-old male. He received 14 cytokine apheresis procedures, for about 4 hours in each session, using a CTR-001 direct hemoperfusion (DHP) cartridge. His serum levels of pro-inflammatory cytokines such as interleukin-6 (IL-6; 1649.1+/-667.1-1257.1+/-489.4 pg/mL, P=0.013) decreased significantly after the CTR-001 procedures. However tumor necrosis factor-alpha (TNF-alpha) (26.2+/-1.7-24.3+/-1.9 pg/mL, P=0.087), IL-1beta (6.1+/-2.9-3.49+/-1.1 pg/mL, P=0.477), IL-8 (192.5+/-33.4-229.5+/-51.8 pg/mL, P=0.754) and IL-10 (14.4+/-2.7-14.0+/-1.9 pg/mL, P=0.726) did not decrease statistically. Therefore, we conclude that in this case, cytokine apheresis using a CTR-001 cartridge was effective for reducing the pro-inflammatory cytokines during severe acute pancreatitis.     

Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options

Serum concentrations of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, and the anti-inflammatory cytokine Il-10, and IL-1 receptor antagonists (IL-1ra) and soluble TNF receptors (sTNFRs) were measured in 65 patients with severe sepsis. All patients were evaluated clinically and microbiologically and were followed up for clinical outcome. Levels of both pro- and anti-inflammatory cytokines were significantly elevated in patients with sepsis. Elevated serum IL-10 and TNF-alpha levels and a high IL-10 to TNF-alpha ratio were associated with death, whereas higher levels of TNF-alpha, IL-6, IL-1ra, and sTNFR were detected in patients with an early hemodynamic deterioration. Interleukin-10 and IL-10:TNF-alpha ratio remained higher in nonsurvivors, whereas IL-10 paralleled the sepsis score. Although both the inflammatory and anti-inflammatory response is profoundly augmented in patients with severe sepsis, the sustained overproduction of the anti-inflammatory cytokine IL-10 is the main predictor of severity and fatal outcome.     

Effect of 5-FU on modulation of disarrangement of immuneassociated cytokines in experimental acute pancreatitis

AIM： To investigate the effects of 5-Fluorouracil （5-FU） on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS： Male Sprague Dawley rats were assigned to 3 Groups： Group A, sham operated rats as controls （n = 7）; Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation （n = 7）, and blood samples were taken for measurement of tumor necrosis factor-α （TNF-α）, interleukin-1 （IL-1）, interleukin-6 （IL-6） （by bioassay）, and interleukin-10 （IL-10）, transforming growth factor-β （TGF-β） （by ELISA）. The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS： Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines （TNF-α, IL-1, IL-6） at the 2 and 6 h period and the anti-inflammatory cytokines （IL-10, TGF-β） at 24 h increased significantly （P 〈 0.05） in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation （P 〈 0.05）, and IL-IO, TGF-13 were inhibited at 24 h compared to Group B （P 〈 0.05）. Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION： 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.     

Monocytes in systematic inflammatory response syndrome： Differences between sepsis and acute pancreatitis

INTRODUCTION Although the knowledge about the underlying pathogenic mechanisms in acute pancreatitis and sepsis has been considerably enriched, comparative studies are lacking. There is evidence that pro-inflammatory cytokine cascade plays a crucial role …     

The oxygen stress index and levels of circulating interleukin-10 and interleukin-6 in patients with chronic heart failure

OBJECTIVES: We sought to study circulating levels of pro- and anti-inflammatory cytokines together with the oxygen stress index in patients with chronic heart failure (CHF). BACKGROUND: Patients with CHF exhibit elevated levels of inflammatory and anti-inflammatory cytokines but the relative level of these cytokines with the oxygen stress index have not been reported. METHODS: Twenty-two patients with CHF and 10 control subjects were studied. Plasma levels of IL-6 and IL-10 were determined and the oxygen stress index was evaluated by urine 8-iso-PGF2alpha estimations. RESULTS: Plasma levels of IL-6 and IL-10 in CHF patients were significantly higher than those observed in the control subjects. Patients with more advanced disease (higher NYHA class) showed higher concentrations of IL-10 and IL-6 than those with less serious disease. 8-iso-PGF2alpha urine concentration (and therefore the oxygen stress index) was significantly higher in patients with CHF in comparison with control subjects. IL-6 plasma levels, but not IL-10 concentrations, correlated significantly with 8-iso-PGF2alpha levels in urine. CONCLUSIONS: Inflammatory and anti-inflammatory cytokine levels, as well as the oxidative stress index, are increased in patients with chronic heart failure. Inflammatory cytokine IL-6, but not anti-inflammatory cytokine Il-10, levels correlated significantly with the oxygen stress index.     

Serum profiles of interleukin-18 in different severity forms of human acute pancreatitis

BACKGROUND: Interleukin 18 (IL-18) is a new mediator and modulator of the immune response; its role in acute pancreatitis (AP), however, has not yet been fully explained. The aim of our study was to evaluate the profile IL-18 serum concentrations in the course of acute pancreatitis. METHODS: The prospective study involves 30 patients with AP (n = 15 with mild AP and n = 15 with severe AP) as well as 10 healthy subjects. AP severity was defined according to Ranson's and Balthazar's criteria, supplemented by serum CRP concentration measurements. In the course of hospitalization, 2 patients with severe AP died. Serum IL-18 and plasma polymorphonuclear leukocyte elastase (PMN-E) concentrations were measured at admission (day 1) and on days 2, 3, 5 and 10. RESULTS: In both the mild and the severe forms of AP, serum IL-18 concentration was significantly higher than in the healthy controls. In severe AP, serum IL-18 reached the highest levels in all observed periods compared to that in patients with mild AP. Significant correlations, calculated for day 1, were found between serum IL-18 and plasma PMN-E (Rs = 0.514. P < 0.001) and between IL-18 and CRP (Rs = 0.463, P < 0.001) levels. CONCLUSIONS: Serum profile IL-18 during AP indicates that this cytokine was released early after AP onset and may play the key role in inflammatory and immune response. Positive correlation between serum IL-18 and commonly known early prognostic markers of AP severity suggest that serum IL-18 concentrations may represent another early marker indicating severe course of AP.     

急性冠状动脉综合征患者白细胞介素-10及白细胞介素-6表达

目的:通过与C反应蛋白(CRP)检测对比,探讨抗炎因子白细胞介素(IL)-10、促炎因子IL-6与急性冠状动脉综合征(ACS)的关系。方法:冠心病患者78例,其中ACS患者40例(ACS组),稳定型心绞痛(SAP组)患者38例,33例胸痛综合征(CPS组)患者作为对照。所有患者均行冠状动脉造影检查。采用ELISA法检测血浆IL-6、IL-10水平,采用免疫比浊法测定CRP值。结果:与SAP组及CPS组相比,ACS组血浆IL-10水平明显降低,IL-6、CRP水平明显升高,差异有统计学意义;SAP组IL-10水平低于CPS组,IL-6、CRP水平高于CPS组,差异无统计学意义;血浆IL-10水平与IL-6及CRP水平呈负相关,IL-6水平与CRP水平正相关。结论:血浆IL-10水平降低和IL-6、CRP值升高对患者ACS的发生有预测价值。抗炎因子和促炎因子水平的失衡是导致斑块不稳定、急性冠状动脉事件发生的重要因素。     

High levels of serum interleukin-10 and tumor necrosis factor-alpha are associated with fatality in fulminant hepatitis

Serum pro- and anti-inflammatory mediators in patients with acute liver diseases were assessed to clarify the clinical significance of these measurements in relation to disease severity. Concentrations of circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, IL-12, and soluble TNF receptors (sTNFR) p55 and p75 were measured at admission in patients with fulminant hepatitis (FH; n=19), severe acute hepatitis (AHS, n=15), or acute hepatitis (AH, n=7). Serum concentrations of TNF-alpha, IL-10, and sTNFR-55 were significantly higher in patients with FH than in those with AHS (P<.05, <.05, and <.01, respectively) or AH (P<.05). Serum IL-10 and TNF-alpha levels were higher in patients who died of FH (n=13) than in FH survivors (n=6; P<.05). The ratios between TNF-alpha and IL-10 and sTNFR-55 or sTNFR-75 were not valuable in predicting mortality and disease severity. However, both proinflammatory cytokine TNF-alpha and anti-inflammatory cytokine IL-10 levels at admission were associated with fatal outcome among patients with FH.     

Reduced levels of transforming growth factor-beta1, interleukin-12 and increased migration inhibitory factor are associated with severe malaria

In the present study, we investigated plasma levels of interleukin (IL)-12 and transforming growth factor (TGF-beta1) in malaria patients as these two cytokines regulate the balance between pro- and anti-inflammatory cytokines. We compared plasma IL-12 and TGF-beta1 levels in groups of malaria patients categorized as uncomplicated, severe, cerebral and placental malaria. Both TGF-beta1 and IL-12 levels were significantly reduced in peripheral plasma of adults with severe and cerebral malaria as well as in plasma of Tanzanian children with cerebral malaria (P<0.05). Similar results were observed with both placental and peripheral plasma of pregnant women who were infected with Plasmodium falciparum. IL-18, a cytokine known to be critical for the induction of IFN-gamma along with IL-1, was produced more in uncomplicated adult patients than in aparasitimic healthy controls (P<0.05). However, IL-18 response rate declined as the symptoms of the disease became more severe suggesting that the IL-18 response may be impaired with increased malaria severity. Together, the results of the three cytokines support the notion that imbalance between pro- and anti-inflammatory cytokines may contribute to the development of severe malaria infection. With malaria infection during pregnancy, we demonstrated that macrophage migration inhibitory factor (MIF) levels in infected placental plasma were significantly higher than those in the paired peripheral plasma (P<0.05). MIF, therefore, may play an important role in the local immune response to placental P. falciparum infection.     

Serum sIL-2r,IL-6, IL-10 and TNF-α level in familial Mediterranean fever patients

 In this study we investigated cytokine levels in patients with familial Mediterranean fever (FMF). Twenty patients and 20 healthy controls were included. Ten patients had acute attacks of FMF, whereas the other 10 were in the silent period. Patients with the acute exacerbation of FMF had higher soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), tumour necrosis factor-α, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen levels than those in the silent period (P<0.001) and controls (P<0.001). In patients with acute attacks of FMF, interleukin-10 (IL-10) levels were not significantly different from those in the other patients or the controls (P>0.05). In FMF patients IL-6, TNF-α, sIL-2r, ESR, CRP and fibrinogen levels increased with the acute-phase reaction, especially in the attack period. On the other hand, anti-inflammatory cytokine IL-10 levels did not increase as much as did the inflammatory cytokines. The balance between the cytokines may help us to understand the pathophysiology of FMF and to develop therapies. We conclude that the levels of the acute-phase reactants and the cytokines could be useful for diagnosis of acute exacerbations, follow-up and treatment. However, the cost of cytokine measurement analyses seems disadvantageous at present. Received: 13 May 2002 / Accepted: 28 October 2002     

Serum lipase, C-reactive protein, and interleukin-6 levels in ERCP-induced pancreatitis

BACKGROUND: C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in acute pancreatitis. Limited studies have evaluated their role in ERCP-induced pancreatitis. The aim of this study was to assess the role of serum lipase, CRP, and IL-6 in ERCP-induced pancreatitis. METHODS: Eighty-five patients (62 women, 23 men; mean age 43 years; range 16-85 years) who underwent ERCP were entered in a prospective trial. ERCP-induced pancreatitis was classified as mild, moderate, or severe. Serum levels of lipase, CRP, and IL-6 were measured before ERCP and at 12 to 24 hours and 36 to 48 hours after ERCP. RESULTS: Mild, moderate, and severe pancreatitis occurred, respectively, in 9, 7, and 4 patients after ERCP. There were significant differences in levels of CRP and IL-6 but not lipase for patients with mild versus moderate and moderate versus severe pancreatitis. The mean CRP levels (mg/dL) at 12 to 24 hours were 0.98 +/- 0.24 in mild pancreatitis, 3.89 +/- 0.32 in moderate pancreatitis, and 12.0 +/- 1.60 in severe pancreatitis. The levels, respectively, at 36 to 48 hours were 1.60 +/- 0.31, 7.60 +/- 0.74, and 25.0 +/- 2.9. The mean IL-6 levels (pg/mL) at 12 to 24 hours were 16.6 +/- 2.06 in mild pancreatitis, 73.0 +/- 15.60 in moderate pancreatitis, and 235.5 +/- 26.31 in severe pancreatitis. The levels at 36 to 48 hours were, respectively, 18.92 +/- 3.28, 100.17 +/- 11.56, and 438.2 +/- 71.50. CONCLUSIONS: Serum CRP and IL-6 levels may be useful early markers for predicting the severity of ERCP-induced pancreatitis.     

Serum Interleukin-10 in Human Acute Pancreatitis

Interleukin 10 (IL-10) recently emerged as anantiinflammatory cytokine that inhibits the secretion ofproinflammatory cytokines by monocytes and/ormacrophages and the release of free oxygen radicals. It has been reported that treatment with IL-10decreases the severity of experimental pancreatitis,mainly by inhibiting cellular necrosis. The aim of thisstudy was to evaluate the behavior of serum IL-10 in patients with acute pancreatitis and toexplore the possibility of a relationship between thiscytokine and severity of the disease. Forty-fivepatients with acute pancreatitis were studied. Acutepancreatitis was of biliary origin in 30 patients, due toalcohol abuse in 10, due to pancreas divisum in 1, andof unknown origin in the remaining 4. According to theBalthazar criteria, 19 patients had scores of A, B, or C and 25 had scores of D or E. Twelvehealthy subjects were also studied as controls. SerumIL-10 was determined in all subjects on admission, andin acute pancreatitis patients also daily for the following four days using a commercial kit.Healthy subjects had no detectable serum levels ofIL-10. In acute pancreatitis patients, serum IL-10levels were increased on the first day of the diseaseand then progressively decrease in the followingdays. On the first day of the acute pancreatitis,patients with the mild disease had serum levels of IL-10significantly higher than those with severe disease, whereas in the following days, no statisticallysignificant difference was observed between the twogroups. The elevation of IL-10 on the first day of theillness is more marked in patients with mild acute pancreatitis than in those with the severe formof the disease. The finding of low values of serum IL-10in severe acute pancreatitis suggests that there may bealtered down-regulation of the immune system response in these patients.     

Prognostic values of IL-6, IL-8, and IL-10 in acute pancreatitis

GOALS: The prognostic importance of interleukin-6 (IL-6), IL-8, and IL-10 in the prediction of acute pancreatitis severity. BACKGROUND: Early assessment of severity in acute pancreatitis could help the patients who are at risk of developing complications. Unfortunately, the used prognostic scoring systems generally are only moderately accurate in assessing disease severity. STUDY: We studied 117 consecutive patients with a diagnosis of acute pancreatitis admitted to our hospital during the past 2 years. Laboratory parameters and cytokines were analyzed from serum taken routinely on admission. Severity criteria were noted for each patient using Ranson, Glasgow, and APACHE II scoring systems. Local and systemic complications, developed during a follow-up period, were classified by Atlanta criteria. RESULTS: IL-6 was the only parameter that statistically significantly predicted complicated acute pancreatitis (P<0.05). IL-8 and IL-10 and the 3 prognostic scoring systems used did not properly assess complicated versus noncomplicated acute pancreatitis. CONCLUSIONS: Our prospective study supported the potential importance of IL-6 in the early assessment of complicated acute pancreatitis, but also suggested that pancreatitis classified as complicated in a large number of patients could not be correctly predicted with the Ranson, Glasgow, and APACHE II scoring systems.     

Significant elevation of serum interleukin-18 levels in patients with acute pancreatitis

Background We have reported that peripheral lymphocyte reduction due to apoptosis is linked to the development of subsequent infectious complications in patients with severe acute pancreatitis and that Th1 (helper T cell type 1)/Th2 (helper T cell type 2) balance tends to cause Th1 suppression in experimental severe acute pancreatitis. It has been reported that interleukin (IL)-18 is a cytokine produced from Kupffer cells and activated macrophages, and that IL-18 acts on Th1 cells and in combination with IL-12 strongly induces production of interferon-γ. However, the role of IL-18 in acute pancreatitis has not yet been fully understood. Methods Serum IL-18 concentrations were determined by an enzyme-linked immunosorbent assay in 43 patients with acute pancreatitis at the time of admission. The relationships with etiology, pancreatic necrosis, severity, blood biochemical parameters on admission, infection, and organ dysfunction during the clinical course and prognosis were analyzed. Results Serum IL-18 levels in patients with acute pancreatitis (656 ± 11pg/ml) were significantly higher than those in healthy volunteers (126 ± pg/ml). Serum IL-18 levels were significantly positively correlated with the Ranson score and Japanese severity score. Among the blood biochemical parameters on admission, base excess and total protein were significantly negatively correlated with serum IL-18 levels. Moreover, the CD4/CD8 rate of lymphocytes, serum IL-6 levels, and serum IL-8 levels were significantly positively correlated with serum IL-18 levels. On day 7 after admission, the CD4/CD8 rate of lymphocytes and the rate of CD4-positive lymphocytes were significantly positively correlated with serum IL-18 levels. Furthermore, serum IL-18 levels in patients with hepatic dysfunction (980 ± 25pg/ml) were significantly higher than those without hepatic dysfunction (464 ± 8pg/ml). Serum IL-18 levels were not related to infection or prognosis. Elevation of serum IL-18 levels continued during 4 weeks after admission. Conclusions These results suggest that serum IL-18 levels are significantly elevated and are correlated with severity in patients with acute pancreatitis and that IL-18 may be closely related to helper T cell response and hepatic dysfunction in this disease.     

Serum interleukin 10 and interleukin 11 in patients with acute pancreatitis

BACKGROUND: Proinflammatory and anti-inflammatory cytokines are involved in the pathogenesis of acute pancreatitis. AIMS: To measure the serial serum levels of interleukin 10 and interleukin 11 in patients with acute pancreatitis and analyse the relation of these anti-inflammatory cytokines to disease severity. METHODS: In 50 patients with acute pancreatitis, the serum concentrations of interleukin 10 and interleukin 11 were determined on days one, two, three, four, and seven after admission. Serum C reactive protein levels were evaluated on days one and two. Severity of pancreatitis was determined according to the Atlanta criteria. RESULTS: Serum concentrations of interleukin 10 on days one to seven were significantly higher in patients with severe pancreatitis than in those with mild pancreatitis. Patients with severe attacks had significantly elevated serum interleukin 11 concentrations on days two to four compared with those with mild attacks, but not on days one and seven. With cut off levels of 30 pg/ml for interleukin 10, 10.5 pg/ml for interleukin 11, and 115 mg/l for C reactive protein, the accuracy rates for detecting severe pancreatitis were 84%, 64%, and 78% respectively on day one and 82%, 74%, and 84% respectively on day two. CONCLUSIONS: Serum interleukin 10 and interleukin 11 concentrations reflect the severity of acute pancreatitis. Interleukin 10 is a useful variable for early prediction of the prognosis of acute pancreatitis.     

Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Inflammatory cytokines may play a pathogenic role in the development of congestive heart failure (CHF). Elevated circulating levels of inflammatory cytokines have been reported in CHF, but most studies have focused on only a few cytokine parameters. However, the activity of these cytokines are modulated by soluble cytokine receptors and cytokines with anti-inflammatory activities, and in the present study several of these interacting factors were examined simultaneously in 38 CHF patients with various degrees of heart failure and in 21 healthy controls. Patients with CHF had increased plasma concentrations of tumor necrosis factor (TNF)alpha, interleukin-6, soluble TNF receptors and the soluble interleukin-6 receptor, glycoprotein (gp)130. They also had elevated ratios of TNFalpha/soluble TNF receptors and interleukin-6/soluble gp130 as well as enhanced interleukin-6 bioactivity in serum, suggesting inflammatory net effects. In addition to raised circulating levels of inflammatory cytokines, CHF patients with severe heart failure also had abnormalities in the levels of anti-inflammatory cytokines, with decreased levels of transforming growth factor beta1 and inadequately raised interleukin-10 in relation to the elevated TNFalpha concentrations. This dysbalance between inflammatory and anti-inflammatory cytokines was also found in monocyte supernatants from CHF patients. The abnormalities in the cytokine network were most pronounced in patients with the most severe heart failure, and several of the immunologic parameters, in particular soluble gp130, were correlated with variables reflecting deranged hemodynamic status. The present study analyzing the complexity of the cytokine network in CHF, demonstrates profound disturbances in the levels of both inflammatory and anti-inflammatory mediators with a marked dysbalance favoring inflammatory effects.