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.     

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.     

Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis.

The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.

Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of interleukin 6

The purpose of this study was to determine the role of interleukin (IL) 6 in mediating the increase in arterial pressure (AP) in response to chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats. AP was higher in RUPP rats (138+/-1 mm Hg) than in normal pregnant (NP) rats (104+/-1 mm Hg). Serum IL-6 levels in the RUPP rats were 104.5+/-28.6 pg/mL as compared with 36.6+/-7.4 pg/mL in NP rats. To determine the long-term effects of a 2- to 3-fold elevation in plasma IL-6 on renal function and AP in pregnant rats, we infused IL-6 for 5 days (2.5 ng/day) in NP rats starting at day 14 of gestation. Five days later, serum IL-6 levels were 55.5+/-6.5 pg/mL in the control NP rats and 157.0+/-36.1 pg/mL in the IL-6-treated NP rats. AP was higher in the IL-6-treated NP rats (115+/-3 mm Hg) as compared with NP controls (101+/-1 mm Hg) at day 19 of gestation. Renal plasma flow and GFR were lower in the IL-6-treated NP rats than in the NP group. IL-6 increased plasma renin activity but did not affect endothelin in IL-6-treated NP rats. In contrast to the NP rats, IL-6 had no effect on AP or renal hemodynamics in virgin rats. In summary, these data indicate that plasma IL-6 is elevated in response to chronic reductions in uterine perfusion in pregnant rats and that a comparable elevation in plasma IL-6 increases AP and reduces renal function in pregnant rats.     

Dietary fat intake and proinflammatory cytokine levels in patients with heart failure

BACKGROUND: Dietary fat intake affects proinflammatory cytokine levels of healthy adults. Whether dietary fats have similar effects in patients with heart failure (HF) is unknown. The purposes of this study were to determine (1) effect of dietary fat on interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and soluble receptors sTNF-R1 and sTNF-R2 levels in patients with HF and (2) subsequent impact of these levels on event-free survival. METHODS AND RESULTS: Forty-two patients provided 4-day food diaries and blood for cytokines. Event-free survival curves were calculated by Kaplan-Meier method and groups compared using log-rank test. IL-6 was not related to fat intake. TNF-alpha levels were elevated in patients with diets higher versus lower in saturated (6.9 +/- 5 versus 4.2 +/- 2 pg/mL) and trans fats (6.8 +/- 4.5 versus 4.5 +/- 2.8 pg/mL). Patients consuming diets higher in polyunsaturated fats had lower sTNF-R1 (2391 +/- 1010 versus 3373 +/- 2098 pg/mL) and sTNF-R2 (3803 +/- 1187 versus 5974 +/- 3275 pg/mL) levels. Higher omega-3 intake produced similar results: sTNF-R1 (2323 +/- 1304 versus 3307 +/- 1973) and sTNF-R2 (4117 +/- 2646 versus 5409 +/- 2801). Event-free survival was decreased in patients with higher TNF-alpha and sTNF-R1 levels. CONCLUSION: Dietary fat intake may affect proinflammatory cytokine levels in patients with HF. Research to determine whether changing composition of dietary fat can alter proinflammatory cytokine activity of HF patients is warranted.     

Effect of resveratrol on activation of nuclear factor kappa-B and inflammatory factors in rat model of acute pancreatitis

AIM: To observe the effect of resveratrol on nuclear factor Kappa-B (NF-κB) activation and the inflammatory response in sodium taurocholate-induced pancreatitis in rats. METHODS: Seventy-two male SD rats were randomly divided into three groups: sham operation group (control), severe acute pancreatitis (SAP) group, and severe acute pancreatitis group treated with resveratrol (RES). A SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing the pancreatic duct. In Res group, Res was given at 30 mg/kg b.m. intraperitoneally after the SAP model was successfully established. Eight animals from each group were sacrificed at 3, 6 and 12 h after modeling. The expression of NF-κB activation of pancreas was detected by irnmunohistochemical staining, whereas the levels of TNF-α and IL-8 in pancreatic tissues were estimated by radioimrnunoassay. The pathological changes of pancreas and lungs were examined microscopically. RESULTS: Much less hyperemia, edema, dust-colored necrotic focus and soaps were noticed in pancreas in RES group than in SAP group. In RES group, hemorrhage, exudates and infiltration of inflammatory cells in pancreas and interstitial edema, destruction of alveolar wall in lung were significantly less than in SAP group. In the SAP group, the activation of NF-κB in pancreatic tissues was enhanced significantly at any measure point compared with control group (64.23±10.72% vs 2.56±0.65%, 55.86±11.34% vs 2.32±0.42%, 36.23±2.30% vs 2.40±0.36%,P<0.01), TNF-α, IL-8 were also increased and reached their peak at 6 h and then declined. The activation of NF-κB and the levels of TNF-α and IL-8 in RES group were significantly lower than those in SAP group (P<0.01): activation (52.63±9.45% vs 64.23±10.72%, 40.52±8.40% vs 55.86±11.34%, 29.83±5.37% vs 36.23±2.30%), TNF-α (132.76±15.68 pg/mL vs 158.36±12.58 pg/mL, 220.32±23.57 pg/mL vs 247.67± 11.62 pg/mL, 175.68±18.43 pg/mL vs 197.35±12.57 pg/mL) and IL-8 (0.62±0.21 μg/L vs 0.83±0.10 μg/L, 1.10±0.124 μg/L vs1.32±0.18 μg/L, 0.98±0.16 μg/L vs 1.27±0.23μg/L). CONCLUSION: The activation of NF-KB is involved in the inflammatory response of rats with SAP. Resveratrol could effectively inhibit the expression of NF-κB activation, alleviate the severity of SAP through its anti-inflammatory effects and regulate the inflammatory mediators.     

Neurohormonal determinants of peak oxygen uptake in patients with chronic heart failure

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. This study determined whether peak oxygen uptake (VO2) can be predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in 84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8 +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL), and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1 vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P < 0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P < 0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and ANP emerged as significant determinants of peak VO2, independent of patient age (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited activation of neurohormones and proinflammatory cytokines. Among the elevated hormonal and cytokine markers, plasma norepinephrine and ANP levels were independent predictors of exercise capacity.     

Serum interleukin-6 and interleukin-10 in patients with acute pancreatitis: clinical implications

BACKGROUND/AIMS: Cytokines are assumed to play an important role in the pathogenesis of acute pancreatitis, but little is actually known. In this study, we assessed changes in the serum levels of interleukin-6 (IL-6), a proinflammatory cytokine, and interleukin-10 (IL-10), an anti-inflammatory cytokine, in patients with acute pancreatitis. METHODOLOGY: Serum levels of IL-6 and IL-10 were measured in 47 patients with acute pancreatitis and compared with their clinical and laboratory data. Changes of the serum levels of the two cytokines were studied in relation to the severity of acute pancreatitis. In addition, the changes of these cytokines after treatment of severe acute pancreatitis were assessed. RESULTS: 1) The serum IL-6 level showed a significant correlation with markers of the severity of acute pancreatitis, suggesting that IL-6 was a useful indicator of the severity of this disease. 2) The IL-10/IL-6 ratio was significantly lower in patients with severe acute pancreatitis, suggesting that a proinflammatory response was predominant in these patients. 3) The IL-10/IL-6 ratio of the patients with severe acute pancreatitis was significantly increased after treatment, especially in patients who received continuous regional arterial infusion of a protease inhibitor and antibiotics. CONCLUSIONS: The predominant pathological state of patients with severe acute pancreatitis may be altered from the systemic inflammatory response syndrome to the compensatory anti-inflammatory response syndrome by successful treatment.     

Tissue factor in predicted severe acute pancreatitis

AIM: To study tissue factor (TF) in acute pancreatitis and evaluate the role of TF as a predictive marker of severity. METHODS: Forty-nine consecutive patients admitted to Lund University Hospital, fulfilling the criteria of predicted severe acute pancreatitis (AP), were recruited prospectively between 2002 and 2004. Blood samples for TF analyses were drawn at inclusion in the study and 12 h, 1 d and 3 d later. RESULTS: Twenty-seven patients developed mild AP, and 22 patients severe AP. At inclusion in the study, the groups were comparable with respect to gender, aetiology, Acute Physiology and Chronic Health Evaluation Ⅱ score, and duration of pain. At inclusion in the study and at 12 h, TF was higher in the severe AP group (P = 0.035 and P = 0.049, respectively). After 1 and 3 d, no differences in TF levels were noted. Interleukin (IL)-6 was significantly higher in the severe AP group at all of the studied time points. C-reactive protein (CRP) was significantly higher in the AP group at 1 and 3 d. In receiver operating characteristic-curves, the area under the curve (AUC) for TF was 0.679 (P = 0.035) at inclusion in the study, and a cut off level for TF of 40 pg/mL showed a sensitivity of 71% and a specificity of 67%, whereas corresponding AUC for IL-6 was 0.775, P = 0.001, and for CRP was 0.653. IL-6 showed better AUC-values than TF at all time points studied. CONCLUSION: TF-levels are raised early in severe AP. TF as an early predictive marker of severe AP is superior to CRP, but inferior to IL-6.     

Specific immunotherapy effect on interleukin-18 and CD30 serum levels in monosensitized patients with rhinitis.

To clarify the immunologic changes associated with specific immunotherapy (SIT), we analyzed interleukin (IL)-18 and CD30 serum levels in a group of patients with allergic rhinitis before and after SIT. IL-18 is a proinflammatory cytokine that plays an important role in the Th1 response. CD30 is a marker of Th2 lymphocytes. We selected 16 healthy donors (HDs) and 16 patients affected by allergic rhinitis, matched for sex and age. Serum IL-18 and CD30 levels were assayed by an immunoenzymatic method. IL-18 serum levels in the patients were lower than in the HDs before SIT (200.69 +/- 93.48 pg/mL versus 296.50 +/- 66.29 pg/mL; p < 0.05). After SIT, patients showed an increase of serum IL-18 levels (288.69 +/- 146.69 pg/mL versus 200.69 +/- 93.48 pg/mL; p < 0.05). On the contrary, serum CD30 levels were higher in patients before SIT with respect to HDs (14.78 +/- 8.30 IU/mL versus < 1 IU/mL; p < 0.05). SIT caused a decrease of serum CD30 levels in patients who were allergic (5.95 +/- 5.70 IU/mL versus 14.78 +/- 8.30 IU/mL; p < 0.05). In conclusion, in this study we showed for the first time the shift of IL-18 and CD30 production after SIT.     

Analysis of circulating apoptosis mediators and proinflammatory cytokines in patients with idiopathic hypertrophic cardiomyopathy: comparison between nonobstructive and dilated-phase hypertrophic cardiomyopathy

We examined the plasma levels of soluble Fas (sFas) or Fas ligand (sFas-L), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in patients with idiopathic nonobstructive (HNCM) and dilated-phase (DHCM) hypertrophic cardiomyopathy. Patients with idiopathic hypertrophic cardiomyopathy (HCM) may deteriorate to DHCM and the pathogenesis is unknown. The levels of these plasma cytokines were measured by ELISA and echocardiography was performed in 38 HNCM and 11 DHCM patients, and 10 normal subjects. The follow-up period was three years. In HNCM, TNF-alpha (43.3 +/- 45.2 versus 16.9 +/- 4.3 pg/mL) and IL-6 (65.1 +/- 86.4 versus 4.0 +/- 2.1 pg/mL) were slightly higher compared to normal subjects and sFas (3.7 +/- 1.2 versus 2.1 +/- 0.7 ng/mL) increased significantly. sFas (3.9 +/- 1.8), TNF-alpha (79.3 +/- 72.4), and IL-6 (234.1 +/- 135.2) in DHCM were significantly increased and only IL-6 was significantly different from HNCM. sFas-L (0.18 +/- 0.08 versus 0.25 +/- 0.05 ng/mL) in HNCM was significantly decreased, and the decrease was marked in DHCM (0.05 +/- 0.02). In HNCM, TNF-alpha was negatively correlated with fractional shortening (r = -0.432, P = 0.0062) or positively with IL-6 (r = 0.665, P < 0.0001), while sFas-L was negatively correlated with IL-6 (r = -0.580, P < 0.0001). DHCM with high sFas had significantly higher cumulative incidences of worsening heart failure. The Fas/Fas-L system and proinflammatory cytokines may play an important role in the status of HCM and its progression to DHCM.     

Protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis

AIM: To investigate the protective effects and mechanisms of Baicalin and octreotide on renal injury of rats with severe acute pancreatitis (SAP). METHODS: One hundred and eighty SD rats were randomly assigned to the model group, Baicalin-treated group, octreotide-treated group and sham operation group. The mortality, plasma endotoxin level, contents of blood urea nitrogen (BUN), creatinine (CREA), phospholipase A2 (PLA2), nitrogen monoxide (NO), tumor necrosis factor (TNF)-alpha, IL-6 and endothelin-1 (ET-1) in serum, expression levels of renal Bax and Bcl-2 protein, apoptotic indexes and pathological changes of kidney were observed at 3, 6 and 12 h after operation. RESULTS: The renal pathological changes were milder in treated group than in model group. The survival at 12 h and renal apoptotic indexes at 6 h were significantly (P<0.05) higher in treated group than in model group [66.67% vs 100%; 0.00 (0.02)% and 0.00 (0.04)% vs 0.00 (0.00)%, respectively]. The serum CREA content was markedly lower in octreotide-treated group than in model group at 3 h and 6 h (P<0.01, 29.200+/-5.710 micromol/L vs 38.400+/-11.344 micromol/L; P<0.05, 33.533+/-10.106 micromol/L vs 45.154+/-17.435 micromol/L, respectively). The expression level of renal Bax protein was not significantly different between model group and treated groups at all time points. The expression level of renal Bcl-2 protein was lower in Baicalin-treated group than in model group at 6 h [P<0.001, 0.00 (0.00) grade score vs 3.00 (3.00) grade score]. The Bcl-2 expression level was lower in octreotide-treated group than in model group at 6 h and 12 h [P<0.05, 0.00 (0.00) grade score vs 3.00 (3.00) grade score; 0.00 (0.00) grade score vs 0.00 (1.25) grade score, respectively]. The serum NO contents were lower in treated groups than in model group at 3 h and 12 h [P<0.05, 57.50 (22.50) and 52.50 (15.00) micromol/L vs 65.00 (7.50) micromol/L; P<0.01, 57.50 (27.50) and 45.00 (12.50) micromol/L vs 74.10 (26.15) micromol/L, respectively]. The plasma endotoxin content and serum BUN content (at 6 h and 12 h) were lower in treated groups than in model group. The contents of IL-6, ET-1, TNF-alpha (at 6 h) and PLA2 (at 6 h and 12 h) were lower in treated groups than in model group [P<0.001, 3.031 (0.870) and 2.646 (1.373) pg/mL vs 5.437 (1.025) pg/mL; 2.882 (1.392) and 3.076 (1.205) pg/mL vs 6.817 (0.810) pg/mL; 2.832 (0.597) and 2.462 (1.353) pg/mL vs 5.356 (0.747) pg/mL; 16.226 (3.174) and 14.855 (5.747) pg/mL vs 25.625 (7.973) pg/mL; 18.625 (5.780) and 15.185 (1.761) pg/mL vs 24.725 (3.759) pg/mL; 65.10 (27.51) and 47.60 (16.50) pg/mL vs 92.15 (23.12) pg/mL; 67.91+/-20.61 and 66.86+/-22.10 U/mL, 63.13+/-26.31 and 53.63+/-12.28 U/mL vs 101.46+/-14.67 and 105.33+/-18.10 U/mL, respectively]. CONCLUSION: Both Baicalin and octreotide can protect the kidney of rats with severe acute pancreatitis. The therapeutic mechanisms of Baicalin and octreotide might be related to their inhibition of inflammatory mediators and induction of apoptosis. Baicalin might be a promising therapeutic tool for severe acute pancreatitis.     

Elevated levels of interleukin-18 and tumor necrosis factor-alpha in serum of patients with type 2 diabetes mellitus: relationship with diabetic nephropathy

To compare levels of interleukin (IL)-18, tumor necrosis factor-alpha (TNF-alpha), and IL-6 in serum, we studied 151 type 2 diabetes mellitus patients with various degrees of nephropathy, as well as 80 healthy volunteers. IL-18, TNF-alpha, and IL-6 in serum were measured using an enzyme-linked immunosorbent assay (ELISA) with the respective mouse monoclonal antibodies. Significant differences in serum levels of IL-18 and TNF-alpha were observed between the patients and control subjects (IL-18, 278.0 +/- 11.9 pg/mL v 172.8 +/- 7.7 pg/mL, P <.0001; TNF-alpha, 2.41 +/- 0.18 pg/mL v 0.46 +/- 0.18 pg/mL, P <.0001), whereas that of IL-6 was not different between the two groups (0.73 +/- 0.10 pg/mL v 0.65 +/- 0.08 pg/mL, difference not significant [NS]), although patients with nephropathy showed higher levels. In addition, IL-18 levels were increased in diabetic patients with the development of urinary albumin excretion, with the highest found in those with microalbuminuria (<30 micro g/mg creatinine, 252.7 +/- 16.4 pg/mL; 30 to >300 micro g/mg creatinine, 352.7 +/- 35.2 pg/mL; >300 micro g/mg creatinine, 350.0 +/- 16.0 pg/mL). Similarly, TNF-alpha and IL-6 in diabetic patients with microalbuminuria or clinical albuminuria were significantly increased as compared with those without albuminuria (TNF-alpha, 3.20 +/- 0.41 pg/mL v 1.94 +/- 0.18 pg/mL; IL-6, 1.64 +/- 1.11 pg/mL v 0.51 +/- 0.05 pg/mL, P <.05, respectively). These results suggest that serum levels of IL-18, TNF-alpha, and IL-6 may have some etiopathogenic roles in diabetic nephropathy.     

Heparin improves organ microcirculatory disturbances in caerulein-induced acute pancreatitis in rats

AIM: Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis. The aim of the study was to evaluate changes in rnicroperfusion of the pancreas, liver, kidney, stomach,colon, skeletal muscle, and to investigate the influence of heparin on the organ rnicrocirculation in caerulein-induced experimental acute pancreatitis.METHODS: Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein (Cn) (15 μg/kg). The organ microcirculation was measured by laser Doppler flowrnetry. Serum interleukin 6 and hernatocrit levels were analysed.RESULTS: Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs. Heparin administration (2&#215;2.5 mg/kg) improved the rnicrocirculation in pancreas (36.9&#177;4% vs75.9&#177;10%), liver (56.6&#177;6% vs 75.2&#177;16%), kidney (45.1&#177;6% vs79.3&#177;5%), stomach (65.2&#177;8% vs78.1&#177;19%), colon (69.8&#177;6% vs 102.5&#177;19%),and skeletal muscle (59.2&#177;6% vs 77.9&#177;13%). Heparin treatment lowered IL-6 (359.0&#177;66 U/mL vs 288.5&#177;58 U/mL) and hematocrit level (53&#177;4% vs 46&#177;3%).CONCLUSION: Hepadn administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.     

Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without hyperpyrexia

Serum cytokine profiles in patients with Plasmodium vivax malaria who presented with and without hyperpyrexia were compared by a retrospective review of the medical records of the consecutive patients seen at the military hospitals near the demilitarized zone in the Republic of Korea from April 2000 through October 2001. Of 162 male patients studied, 120 (86.4%) presented with hyperpyrexia (i.e., an axillary temperature > or = 40 degrees C). The mean +/- SEM ages of the patients with and without hyperpyrexia were 21.5 +/- 0.14 and 21.9 +/- 0.39 years, respectively (P = 0.33). The mean +/- SEM concentrations of serum interleukin (IL)-6 (379.7 +/- 44.1 pg/mL versus 105.4 +/- 26.8 pg/mL; P = 0.002), IL-10 (583.4 +/- 58.2 pg/mL versus 142.4 +/- 39.7 pg/mL; P = 0.0001), and interferon-gamma (312.6 +/- 33.9 pg/mL versus 112.9 +/- 27.1 pg/mL; P = 0.0001) were significantly higher in patients with hyperpyrexia compared with those without hyperpyrexia. The mean +/- SEM concentrations of serum tumor necrosis factor-alpha were 155.5 +/- 54.5 pg/mL and 109.9 +/- 29.3 pg/mL (P = 0.27) in patients who presented with and without hyperpyrexia, respectively. Further studies are needed to examine whether serum concentrations of these cytokines also parallel their concentrations at the tissue sites of their production and action.     

Elevated IL-6 levels in the synovial fluid of osteoarthritis patients stem from plasma cells

OBJECTIVE: To analyse the levels of interleukin-6 (IL-6) in the synovial fluids and sera of patients with osteoarthritis (OA) and to identify the IL-6-secreting cells. METHODS: Serum, synovial fluid, synovial tissue, and articular cartilage samples were collected from 49 OA patients with end-stage knee or hip OA who underwent joint replacement surgery. Serum and synovial fluid levels of IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) and IL-6-secreting cells were identified by immunohistochemistry. RESULTS: Eight out of 49 patients (16%) exhibited elevated IL-6 levels in the synovial fluids, averaging at 2022+/-526 pg/mL, while the levels in the rest of the patients averaged at 132+/-19 pg/mL. The sera levels of all patients were comparable in the 10 pg/mL range. Immunohistochemical analyses revealed plasma cells in the synovial lining of the high producers as the source of IL-6. CONCLUSIONS: Synovial fluid IL-6 levels may help to classify OA patients and may point to a subgroup with a particular impact from their immune system.     

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.     

Hemoconcentration is a poor predictor of severity in acute pancreatitis

AIM: To determine whether the hematocrit (Hct) at admission or at 24 h after admission was associated with severe acute pancreatitis (AP), organ failure (OF), and pancreatic necrosis. METHODS: A total of 336 consecutive patients with a first AP episode were studied. Etiology, Hct values at admission and at 24 h, development of severe AP according to Atlanta's criteria, pancreatic necrosis, OF and mortality were recorded. Hemoconcentration was defined as Hct level >44% for males and >40% for females. The t-test and X2 test were used to assess the association of hemoconcentration to the severity, necrosis and OF. Diagnostic accuracy was also determined. RESULTS: Biliary disease was the most frequent etiology (n = 148). Mean Hct levels at admission were 41±6% for females and 46±7% for males (P<0.01). Seventy-eight (23%) patients had severe AP, and OF developed in 45 (13%) patients. According to contrast-enhanced computed tomography scan, 36% (54/150) patients showed pancreatic necrosis. Hct levels were elevated in 58% (55/96) and 61% (33/54) patients with interstitial and necrotizing pancreatitis, respectively. Neither Hct levels at admission nor hemoconcentration at 24 h were associated with the severity, necrosis or OF. Sensitivity, specificity and positive predictive values for both determinations were very low; and negative predictive values were between 61% and 86%, being the highest value for OF. CONCLUSION: Hct is not a useful marker to predict a worse outcome in acute pancreatitis. In spite of the high negative predictive value of hemoconcentration, the prognosis gain is limited due to an already high incidence of mild disease.     

Interleukin-6 and thyroid hormone metabolism in pediatric cardiac surgery patients.

Pediatric patients undergoing cardiac surgery have been reported to have low serum triiodothyronine (T(3)) levels in the postoperative period. The cause of this dysfunction is not known, although proinflammatory cytokines such as interleukin-6 (IL-6) have been implicated in the inhibition of hepatic conversion of thyroxine (T(4)) to T(3). This study measured serum levels of IL-6 and T(3) during the first 4 postoperative days in 16 children (mean age, 28 +/- 7 days) undergoing cardiopulmonary bypass surgery. The mean preoperative serum total T(3) level was 164 +/- 30 ng/dL (2.5 +/- 0.5 nmol/L) that decreased significantly to a nadir of 43 +/- 8 ng/dL (0.6 +/- 0.01 nmol/L) within 48 hours after surgery. Serum IL-6 levels increased significantly from 16 +/- 7 pg/mL preoperatively to a peak value of 374 +/- 134 pg/mL measured 2-3 hours after surgery. A positive correlation (r(2) = 0.507) was found between the peak serum level of IL-6 and the lowest serum T(3) level in each patient attained during the 4 postoperative days. Potential treatments directed toward diminishing the rise in proinflammatory cytokines in the immediate postoperative period may prove effective in preventing the low serum T(3) in children undergoing cardiac surgery, and thus diminish the associated postoperative morbidity.