TNF-α as a therapeutic target in acute pancreatitis - Lessons from experimental models

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)431-448
Number of pages18
JournalTheScientificWorldJournal
Volume7
DOIs
Publication statusPublished - Mar 30 2007

Fingerprint

tumor
Pancreatitis
Theoretical Models
Tumor Necrosis Factor-alpha
Acute Lung Injury
Liver Failure
Liver
serum
inhibitor
Shock
Animals
Therapeutics
Animal Models
Research Personnel
Clinical Trials
Inflammation
damage
animal
Serum
Population

Keywords

  • Anti-TNF-α therapy
  • Clinical trial
  • Cytokines
  • Experimental pancreatitis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Medicine(all)

Cite this

TNF-α as a therapeutic target in acute pancreatitis - Lessons from experimental models. / Malleo, Giuseppe; Mazzon, Emanuela; Siriwardena, Ajith K.; Cuzzocrea, Salvatore.

In: TheScientificWorldJournal, Vol. 7, 30.03.2007, p. 431-448.

Research output: Contribution to journalArticle

Malleo, Giuseppe ; Mazzon, Emanuela ; Siriwardena, Ajith K. ; Cuzzocrea, Salvatore. / TNF-α as a therapeutic target in acute pancreatitis - Lessons from experimental models. In: TheScientificWorldJournal. 2007 ; Vol. 7. pp. 431-448.
@article{03a6d55aaefb4b0bb1e6db0533f4881b,
title = "TNF-α as a therapeutic target in acute pancreatitis - Lessons from experimental models",
abstract = "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.",
keywords = "Anti-TNF-α therapy, Clinical trial, Cytokines, Experimental pancreatitis",
author = "Giuseppe Malleo and Emanuela Mazzon and Siriwardena, {Ajith K.} and Salvatore Cuzzocrea",
year = "2007",
month = "3",
day = "30",
doi = "10.1100/tsw.2007.98",
language = "English",
volume = "7",
pages = "431--448",
journal = "The Scientific World Journal",
issn = "2356-6140",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - TNF-α as a therapeutic target in acute pancreatitis - Lessons from experimental models

AU - Malleo, Giuseppe

AU - Mazzon, Emanuela

AU - Siriwardena, Ajith K.

AU - Cuzzocrea, Salvatore

PY - 2007/3/30

Y1 - 2007/3/30

N2 - 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.

AB - 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.

KW - Anti-TNF-α therapy

KW - Clinical trial

KW - Cytokines

KW - Experimental pancreatitis

UR - http://www.scopus.com/inward/record.url?scp=34047226686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047226686&partnerID=8YFLogxK

U2 - 10.1100/tsw.2007.98

DO - 10.1100/tsw.2007.98

M3 - Article

VL - 7

SP - 431

EP - 448

JO - The Scientific World Journal

JF - The Scientific World Journal

SN - 2356-6140

ER -