Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications.
Curr Drug Targets Inflamm Allergy
; 1(4): 393-403, 2002 Dec.
Article
en En
| MEDLINE
| ID: mdl-14561185
ABSTRACT
Severe acute pancreatitis causes a high incidence of mortality due to the systemic inflammatory response syndrome leading to multiple organ failure. At present, there is no treatment against severe acute pancreatitis, other than supportive critical care. The relationship between pancreatic injury and the uncontrolled systemic response is not completely understood. Nevertheless, experimental and clinical evidences have shown that pro-inflammatory cytokines and oxidative stress are critically involved in the development of local and systemic complications associated with severe acute pancreatitis. Serum levels of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta, increase during the course of acute pancreatitis and they appear to be the driving force for the initiation and propagation of the systemic response. Accordingly, pretreatment with an antibody against TNF-alpha or blockade of TNF-alpha production with pentoxifylline ameliorates experimental acute pancreatitis. In addition, serum IL-6 and IL-8 levels appear to be correlated with severity of pancreatic inflammation. The role of oxidative stress in acute pancreatitis has been evidenced indirectly by beneficial effects of antioxidants as well as directly by pancreatic glutathione depletion and increased lipid peroxidation. Furthermore, circulating xanthine oxidase released by the damaged pancreas acts as a source of systemic oxidative stress contributing to lung inflammation. In conclusion, pancreatic injury seems to trigger at least two different pathways, i.e. pro-inflammatory cytokines and oxidative stress, both involved in the systemic effects of acute pancreatitis. Elucidation of these mechanisms and their interactions is critical to develop a treatment based on the pathophysiology of acute pancreatitis.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pancreatitis
/
Citocinas
/
Estrés Oxidativo
Tipo de estudio:
Etiology_studies
Límite:
Humans
Idioma:
En
Revista:
Curr Drug Targets Inflamm Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2002
Tipo del documento:
Article
País de afiliación:
España