Soluble receptors released during acute pancreatitis interfere with the detection of tumor necrosis factor-α

Folch, Emma; Serrano, Anna; Sabater, Lluis; Gelpí, E.; Roselló‐Catafau, Joan; Closa, Daniel

doi:10.1097/00003246-200105000-00029

Cited by 14 publications

(12 citation statements)

References 15 publications

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“…While this has also been attributed to interference of the soluble TNF receptor with the detection of TNF· [30], the findings of the present study indicate that circulating TNF· does not increase following the induction of pancreatitis, and furthermore, that TNF· levels were significantly lower in rats with severe pancreatitis compared to sham operated controls. In our study we used a competitive ELISA to measure total TNF· and therefore rule out interference with the soluble receptor.…”

Section: Discussioncontrasting

confidence: 64%

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Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis

et al. 2005

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Background: Release of TNFα is thought to play an important role in mediating systemic effects in acute pancreatitis (AP). We have been unable to find an elevation of plasma TNFα in AP and hypothesize that it is susceptible to catabolism by circulating pancreatic proteases. Methods: (1) AP was induced in Sprague-Dawley rats by cerulein hyperstimulation preceded by intraductal infusion of saline (mild) or glycodeoxycholic acid (severe). Healthy and sham-operated animals served as controls. Severity of pancreatitis was confirmed by histology. Plasma TNFα levels were measured at various time points after induction of AP with competitive ELISA. (2) Recombinant rat TNFα (rrTNFα) was incubated with trypsin, elastase, chymotrypsin and pepsin. Western Blot was performed to visualize TNF degradation. (3) RrTNFα was incubated in a concentration and time-dependant manner with proteases and TNF bioactivity was evaluated with a cytotoxicity assay. Results: (1) Plasma TNFα levels in severe pancreatitis were significantly lower than in sham-operated controls after 0.5 and 6 h. (2) Incubation with proteases showed degradation in the presence of trypsin, elastase and chymotrypsin and no effect of pepsin. (3) There was a concentration dependent inactivation of rrTNFα in the presence of pancreatic proteases and a complete time-dependent inactivation in the presence of trypsin. Conclusion: Plasma TNFα does not rise in experimental AP, and levels are significantly lower in severe pancreatitis compared to sham-operated controls. Our study demonstrates degradation and inactivation of TNFα by pancreatic proteases, suggesting that it is unlikely it plays an important role in the development of distant organ failure.

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Section: Discussioncontrasting

confidence: 64%

“…In our study we used a competitive ELISA to measure total TNF· and therefore rule out interference with the soluble receptor. Folch et al [30] recommend the use of a competitive ELISA for the measurement of this cytokine, which detects free and receptor bound TNF·. They validated the use of this particular assay for rat TNF·.…”

Section: Discussionmentioning

confidence: 99%

Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis

et al. 2005

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“…viously been shown (Folch et al, 2001;Frossard et al, 2002a). When mice were treated with cerulein, TNF-␣ RI concentrations increased in serum and in pancreatic and lung tissues (Fig.…”

Section: Pastor Et Almentioning

confidence: 83%

Role of Macrophage Inflammatory Peptide-2 in Cerulein-Induced Acute Pancreatitis and Pancreatitis-Associated Lung Injury

Pastor

Rubbia‐Brandt

Hadengue

et al. 2003

Laboratory Investigation

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SUMMARY:Acute pancreatitis is an inflammatory process of variable severity, and leukocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The effects of mediators released by these inflammatory cells may induce tissue damage. The aim of our study was to evaluate the role of the chemokine, macrophage inflammatory protein-2 (MIP-2), in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. The severity of pancreatitis was measured by serum amylase, pancreatic edema, acinar cell necrosis, and myeloperoxidase activity. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. To determine the role of MIP-2 in the pathophysiology of the disease, anti-MIP-2 antibody was administered either 1 hour before or 2 hours after the start of cerulein administration. MIP-2 concentrations increased in serum, pancreas, and lung tissues in mice treated with cerulein. Anti-MIP-2 antibody administrated either before or after cerulein partially protected against pancreas and lung injury. These results show that MIP-2 plays a key role in the pathophysiology of acute pancreatitis and that MIP-2 blockade may improve the outcome of the disease. (Lab Invest 2003, 83:471-478).

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Section: Role Of Cytokines and Other Inflam-matory Mediators In The Imentioning

confidence: 99%

“…The presence of such receptors could interfere with the measurement of serum TNF-α levels [30]. Hence, serum levels of total TNF-α (free plus bound to receptor) should be measured instead of free TNF-α levels to follow the evolution of TNF-α production [30]. In addition, plasma concentrations of soluble TNF-α receptors have been correlated with the development of multiple organ failure, since they were significantly higher in patients with this severe response than in those without it [31].…”

Section: Role Of Cytokines and Other Inflam-matory Mediators In The Imentioning

confidence: 99%

Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis

Pereda

Sabater²,

Aparisi³

et al. 2006

CMC

130

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Acute pancreatitis is an inflammation initially localized in the pancreatic gland which may lead to local and systemic complications. The development of severe acute pancreatitis is mediated by pathophysiological mechanisms involved in the systemic inflammatory response, cytokines and oxidative stress being their components of major importance. Nevertheless, it is still unknown why an episode of acute pancreatitis remains mild or progresses to a severe form. Activated leukocytes are the main source of cytokines. Interleukin 1beta and tumor necrosis factor alpha (TNF-alpha) initiate and propagate almost all the consequences of the systemic inflammatory response syndrome, leading to amplification of the inflammatory response. It is noteworthy that the systemic inflammatory response is restrained and the rate of mortality decreased in acute pancreatitis when TNF-alpha is blocked with specific antibodies or in knock-out mice deficient in its receptors. A synergy between pro-inflammatory cytokines and oxidative stress occurs in the development of the inflammatory response in acute pancreatitis. Pro-inflammatory cytokines and oxidative stress trigger common signal transduction pathways that lead to amplification of the inflammatory cascade, mainly through activation of mitogen-activated protein kinases (MAPK) and nuclear factor kappaB (NF-kappaB). Furthermore, pro-inflammatory cytokines, particularly TNF-alpha, and oxidative stress promote each other generating a vicious circle in acute pancreatitis. This cross-talk that arises between pro-inflammatory cytokines and oxidative stress greatly contributes to amplification of the uncontrolled inflammatory cascade through MAPK and NF-kappaB.

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Soluble receptors released during acute pancreatitis interfere with the detection of tumor necrosis factor-α

Abstract: Circulating soluble receptor of tumor necrosis factor-alpha could interfere with the detection of tumor necrosis factor-alpha in some pathologies, such as pancreatitis, that are associated with increases in soluble receptor of tumor necrosis factor-alpha.

Cited by 14 publications

References 15 publications

Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis

Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis

Role of Macrophage Inflammatory Peptide-2 in Cerulein-Induced Acute Pancreatitis and Pancreatitis-Associated Lung Injury

Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis

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