Role of tumor necrosis factor-α in acute pancreatitis: From biological basis to clinical evidence

Giuseppe Malleo, Emanuela Mazzon, Ajith K. Siriwardena, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine that exerts host-damaging effects in different autoimmune and inflammatory diseases. It is a key regulator of other proinflammatory cytokines and of leukocyte adhesion molecules, and it is a priming activator of immune cells. In recent years, several research lines-mostly derived from animal models and in vitro studies-suggested that TNF-α plays a pivotal role in the pathogenesis of acute pancreatitis. In particular, it contributes to the systemic progression of the inflammatory response and to the end-organ dysfunction often observed in severe disease. Current clinical applications of TNF-α in acute pancreatitis include the assessment of blood concentrations to predict disease severity and to identify individuals prone to develop complications such as multiple organ failure and septic shock. However, TNF-α is rapidly cleared from the bloodstream, and sensitivity and overall accuracy of its measurement seem strictly time dependent, thereby being of potential prognostic value only in the first days after the onset of the disease. In parallel, TNF-α has been evaluated as a novel pharmacologic target for treating pancreatitis. Although promising results have been observed in the laboratory, transition to clinical practice seems problematic, in particular, in the light of divergent results obtained in sepsis trials. Therefore, in future clinical trials pertaining to TNF-α neutralization in acute pancreatitis, timing of intervention should be related to changes in TNF-α serum levels, and inclusion and exclusion criteria should be accurately selected to better define the population most likely to benefit.

Original languageEnglish
Pages (from-to)130-140
Number of pages11
JournalShock
Volume28
Issue number2
DOIs
Publication statusPublished - Aug 2007

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Keywords

  • Clinical trial
  • Cytokines
  • Experimental pancreatitis
  • Multiple organ failure
  • TNF-α neutralization

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

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