scholarly journals TNF-α as a Therapeutic Target in Acute Pancreatitis — Lessons from Experimental Models

2007 ◽  
Vol 7 ◽  
pp. 431-448 ◽  
Author(s):  
Giuseppe Malleo ◽  
Emanuela Mazzon ◽  
Ajith K. Siriwardena ◽  
Salvatore Cuzzocrea
Keyword(s):  
Acute Pancreatitis ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Organ Damage ◽  
Experimental Models ◽  
Clinical Applications ◽  
Inclusion Criteria ◽  
Tnf Α ◽  
Considerable Body ◽  
Necrosis Factor

A considerable body of experimental evidence suggests that tumor necrosis factor (TNF)-α plays a major role in several aspects of inflammation and shock. In particular, it is pivotal in many detrimental effects of acute pancreatitis, and it represents a major determinant of the systemic progression and end-organ damage (such as acute lung injury and liver failure) of this pathologic condition. Given the importance of TNF-α in the pathogenesis of acute pancreatitis, investigators have regarded blocking the action of this mediator as an attractive treatment option. Different specific and nonspecific inhibitors have been developed with promising results in animal models, but, on the other hand, no clinical trials have been designed so far. Difficulties in clinical applications may be multifactorial; experimental models are not fully reliable and reproduce at least some aspects of human disease, timing of intervention should be related to changes in TNF-α serum levels, and inclusion criteria should be accurately selected to better define the population most likely to benefit.

Serum levels of interleukin 6 and tumor necrosis factor-α in hyperthyroid patients before and after propylthiouracil treatment

1995 ◽  
Vol 132 (6) ◽  
pp. 668-672 ◽  
Author(s):  
Ismail Çelik ◽  
Sema Akalin ◽  
Tomris Erbaş
Keyword(s):  
Tumor Necrosis Factor ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Serum Levels ◽  
Graves Disease ◽  
Tnf Α ◽  
Factor Α ◽  
Hyperthyroid Patients ◽  
Necrosis Factor

Çelik I, Akalin S, Erbaş T. Serum levels of interleukin 6 and tumor necrosis factor-α in hyperthyroid patients before and after propylthiouracil treatment. Eur J Endocrinol 1995;132:668–72. ISSN 0804–4643 Contrary to the usual inhibitory role of tumor necrosis factor-α (TNF-α) thyroid metabolism, it also has specific stimulatory effects in autoimmune thyroid disorders, including induction of HLA class II antigen-presenting cell—T cell interaction. Despite high intrathyroidal concentrations, various studies were not able to demonstrate high serum levels of TNF-α in patients with Graves' disease. To investigate this discrepancy we determined TNF-α and interleukin 6 (IL-6) levels in 25 hyperthyroid patients who responded to propylthiouracil treatment (16 with Graves' disease and nine with toxic multinodular goiter) and compared them with the levels found in euthyroid patients with simple diffuse goiter (n = 15) and normal healthy controls (n = 15). Median IL-6 levels were high in both Graves' disease and toxic multinodular goiter patients before propylthiouracil treatment (23 and 26.5 pg/ml, respectively). After restoring euthyroidism there was a statistically significant decline to near-normal levels (3 and 10 pg/ml, respectively). On the other hand, median serum TNF-α levels were high only in Graves' disease patients (20 pg/ml) and could not be normalized with antithyroid medication (20 pg/ml) compared to that of controls (5 pg/ml). Tumor necrosis factor-α, but not IL-6, was found to be high in the sera of Graves' disease patients when euthyroid, which may be due to an ongoing antigen–antibody interaction, a feature of autoimmune attack. It remains to be determined whether the degree of TNF-α and/or IL-6 elevation will be a predictor of disease recurrence. Ismail Çelik, Section of Oncology, Dept. of Medicine, Hacettepe University Institute of Oncology, Ankara 06100, Turkey

scholarly journals Tumor necrosis factor-α: regulation of renal function and blood pressure

2013 ◽  
Vol 304 (10) ◽  
pp. F1231-F1242 ◽  
Author(s):  
Vanesa D. Ramseyer ◽  
Jeffrey L. Garvin
Keyword(s):  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Immune Cell ◽  
Organ Damage ◽  
Physiological Status ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that becomes elevated in chronic inflammatory states such as hypertension and diabetes and has been found to mediate both increases and decreases in blood pressure. High levels of TNF-α decrease blood pressure, whereas moderate increases in TNF-α have been associated with increased NaCl retention and hypertension. The explanation for these disparate effects is not clear but could simply be due to different concentrations of TNF-α within the kidney, the physiological status of the subject, or the type of stimulus initiating the inflammatory response. TNF-α alters renal hemodynamics and nephron transport, affecting both activity and expression of transporters. It also mediates organ damage by stimulating immune cell infiltration and cell death. Here we will summarize the available findings and attempt to provide plausible explanations for such discrepancies.

scholarly journals Comparative study of the therapeutic potential of octreotide versus trimetazidine and their combination on acute pancreatitis in male rats

2018 ◽  
Vol 4 (4) ◽  
Keyword(s):  
Acute Pancreatitis ◽  
Therapeutic Potential ◽  
Serum Levels ◽  
Male Rats ◽  
Combination Group ◽  
Mortality And Morbidity ◽  
Tnf Α ◽  
Total Antioxidant ◽  
Factor Α ◽  
Necrosis Factor

Objective Acute pancreatitis continues to be associated with significant rates of mortality and morbidity, and therapeutic options are stillvery limited. Various theories have been suggested regarding the pathophysiology of acute pancreatitis, lot of research into differentmedical treatments for the treatment of acute pancreatitis, but it is not clear what benefits each treatment has, or indeed if any medicaltreatment is beneficial apart from supportive treatment.Aim To clarify the potential therapeutic effect of octreotide, trimetazidine, and their combination in acute pancreatitis.Methods Acute pancreatitis was induced by L-arginine and treated with octreotide subcutaneously, trimetazidine intraperitoneally andcombination therapy by octreotide and trimetazidine. The rats were followed for 24 h. At the 24th hour we determined serum levels oftumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), total antioxidant capacity (TAC), lipase, and amylase, and the pancreatic tissues wereanalyzed histopathologically.Results TNF-α (P < 0.001), IL-1β (P < 0.001), TAC (P < 0.001), lipase (P < 0.001), and amylase (P < 0.001) serum levels and scores ofhistopathological changes (P < 0.05) were significantly lower in combination group as compared with both octreotide and trimetazidinegroups.Conclusion Combination treatment markedly decreases biochemical and histopathological changes in acute pancreatitis, thus amelioratepancreatic injury in l-arginine induced acute pancreatitis.

scholarly journals Is there a therapeutic window for pentoxifylline after the onset of acute pancreatitis?

2012 ◽  
Vol 27 (7) ◽  
pp. 487-493 ◽  
Author(s):  
Ana Maria Mendonça Coelho ◽  
Tiago Alexandre Kunitake ◽  
Marcel Cerqueira Cesar Machado ◽  
Joilson Oliveira Martins ◽  
Rosely Antunes Patzina ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Saline Solution ◽  
Serum Levels ◽  
Saline Group ◽  
Therapeutic Window ◽  
Enzyme Linked Immunosorbent Assay ◽  
Myeloperoxidase Activity ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Necrosis Factor

PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.

scholarly journals Inflammatory Profile and Response to Anti-Tumor Necrosis Factor Therapy in Patients with Chronic Pulmonary Sarcoidosis

2011 ◽  
Vol 18 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Matthew J. Loza ◽  
Carrie Brodmerkel ◽  
Roland M. Du Bois ◽  
Marc A. Judson ◽  
Ulrich Costabel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Serum Levels ◽  
Unknown Etiology ◽  
Infliximab Treatment ◽  
Tnf Α ◽  
Associated Proteins ◽  
Inflammatory Profile ◽  
Necrosis Factor

ABSTRACTSarcoidosis is an inflammatory, granulomatous disease of unknown etiology that most commonly afflicts the lungs. Despite aggressive immunosuppressive therapies, many sarcoidosis patients still chronically present significant symptoms. Infliximab, a therapeutic tumor necrosis factor alpha (TNF-α) monoclonal antibody (MAb), produced a small but significant improvement in forced vital capacity (FVC) in sarcoidosis patients in a double-blind, placebo-controlled, phase II clinical trial. In the current study, serum samples from this clinical trial were assessed to evaluate the underlying hypothesis that treatment with infliximab would reduce systemic inflammation associated with sarcoidosis, correlating with the extent of clinical response. A 92-analyte multiplex panel was used to assess the expression of serum proteins in 134 sarcoidosis patients compared with sera from 50 healthy controls. A strong systemic inflammatory profile was associated with sarcoidosis, with 29 analytes significantly elevated in sarcoidosis (false-discovery rate, <0.05 and >50% higher than controls). The associated analytes included chemokines, neutrophil-associated proteins, acute-phase proteins, and metabolism-associated proteins. This profile was evident despite patients receiving corticosteroids and immunosuppressive therapies. Following infliximab treatment, sarcoidosis patients expressing the highest levels of TNF-α, who had more severe disease, had the greatest improvement in FVC and reduction in serum levels of the inflammatory proteins MIP-1β and TNF-RII. This study supports the need for further exploration of anti-TNF therapy for chronic sarcoidosis patients, particularly for those expressing the highest serum levels of TNF-α.

Effect of Hypothermia on Serum Myelin Basic Protein and Tumor Necrosis Factor-α in Neonatal Hypoxic-Ischemic Encephalopathy

2021 ◽  
Author(s):  
Qiuli Wang ◽  
Hongyan Lv ◽  
Sujing Wu ◽  
Junxia Song ◽  
Junqin Li ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Basic Protein ◽  
Serum Levels ◽  
Control Group ◽  
Tnf Α ◽  
Hypothermia Group ◽  
Neurodevelopmental Impairment ◽  
Factor Α ◽  
Ischemic Encephalopathy ◽  
Necrosis Factor

Objective Multiple randomized controlled trials have shown that hypothermia is a safe and effective treatment for neonatal moderate or severe hypoxic-ischemic encephalopathy (HIE). The neuroprotective mechanisms of hypothermia need further study. The aim of this study was to investigate the effect of hypothermia on the serum levels of myelin basic protein (MBP) and tumor necrosis factor-α (TNF-α) as well as neurodevelopmental outcomes in neonatal HIE. Study Design Eighty-five neonates with moderate-to-severe HIE were divided into a hypothermia group (n = 49) and a control group (n = 36). Serum levels of MBP and TNF-α within 6 hours after birth and after 3 days of treatment were determined by enzyme-linked immunosorbent assay, and neurodevelopmental outcome at the age of 12 to 15 months was assessed by using the Gesell development scale. Results After 3 days of treatment, serum levels of MBP and TNF-α in the control group were not significantly different from levels before treatment (p > 0.05), and serum levels of MBP and TNF-α in the hypothermia group were significantly lower than levels before treatment (p < 0.05). Serum levels of MBP and TNF-α were significantly negatively correlated with developmental quotient (DQ; r =  − 0.7945, p = 0.0000; r =  − 0.7035, p = 0.0000, respectively). Serum levels of MBP and TNF-α in neurodevelopmentally impaired infants were significantly higher than those in infants with suspected neurodevelopmental impairment and those in neurodevelopmentally normal infants (both p < 0.01). The rate of reduction of neurodevelopmental impairment was higher among infants in the hypothermia group than among those in the control group (χ2 = 16.3900, p < 0.05). Conclusion Hypothermia can reduce serum levels of MBP and TNF-α in neonates with HIE. Inhibiting the release of TNF-α may be one of the mechanisms by which hypothermia protects the myelin sheath. Key Points

scholarly journals Do the Changes in the Serum Levels of IL-2, IL-4, TNFα, and IL-6 Reflect the Inflammatory Activity in the Patients with Post-ERCP Pancreatitis?

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Guldem Kilciler ◽  
Ugur Musabak ◽  
Sait Bagci ◽  
Zeki Yesilova ◽  
Ahmet Tuzun ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Tumor Necrosis ◽  
Clinical Laboratory ◽  
Major Complication ◽  
Serum Levels ◽  
Inflammatory Activity ◽  
Serum Concentrations ◽  
Endoscopic Retrograde ◽  
Therapeutic Ercp ◽  
Necrosis Factor

Background. Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits.Goals. To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)α, and IL-6 levels and the development of post-ERCP pancreatitis.Study. Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFα, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP.Results. Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFαlevels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFα/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP.Conclusions. The enhancement of serum TNFαand IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP.

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