Role of tumor necrosis factor-alpha in acute pancreatitis: from biological basis to clinical evidence.
Tumor necrosis factor (TNF)-alpha 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-alpha 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-alpha 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-alpha 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-alpha 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-alpha neutralization in acute pancreatitis, timing of intervention should be related to changes in TNF-alpha serum levels, and inclusion and exclusion criteria should be accurately selected to better define the population most likely to benefit.
Malleo
Giuseppe
G
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Via C. Valeria-Gazzi, 98100 Messina, Italy.
Mazzon
Emanuela
E
Siriwardena
Ajith K
AK
Cuzzocrea
Salvatore
S
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers; D006801:Humans; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha