Absence of endogenous interleukin-6 enhances the inflammatory response during acute pancreatitis induced by cerulein in mice

被引:52
作者
Cuzzocrea, S
Mazzon, E
Dugo, L
Centorrino, T
Ciccolo, A
McDonald, MC
De Sarro, A
Caputi, AP
Thiemermann, C
机构
[1] Univ Messina, Sch Med, Inst Pharmacol, Torre Biol,Policlin, I-98100 Messina, Italy
[2] Univ Messina, Sch Med, Dept Biomorphol, I-98100 Messina, Italy
[3] Univ Messina, Inst Gen Surg, I-98100 Messina, Italy
[4] William Harvey Res Inst, London EC1M 6BQ, England
关键词
IL-6; peroxynitrite; pancreatitis; free radicals; inflammation; poly (ADP-ribose) polymerase;
D O I
10.1006/cyto.2002.0883
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin-6 (IL-6) exerts a wide spectrum of regulatory activities during immune and inflammatory responses. The aim of this study was to investigate the role of endogenous IL-6 in the inflammatory response associated with acute pancreatitis. Acute pancreatitis was induced by hourly (x 5) i.p. injections of cerulein (50 mug/kg, suspended in saline solution) in IL-6 deficient mice (IL-6-KO) and wild-type (IL-6WT) littermates. IL-6KO mice exhibited a more severe tissue injury and a higher rate of mortality and when compared to IL-6WT mice. Acute pancreatitis was characterized by edema, neutrophil infiltration, tissue hemorrhage and cell necrosis, upregulation of P-selectin and intercellular adhesion molecule-1 (ICAM-1), as IN-ell as increases in the serum levels of amylase and lipase. The degree of oxidative and nitrosative tissue damage was significantly greater in IL-6KO mice than in wild-type littermates, as indicated by higher tissue levels of malondialdehyde and nitrosylated proteins. Plasma levels of the inflammatory cytokines tumour necrosis factor-alpha and interleukin-1beta were also greatly, enhanced in IL-6KO mice when compared to wild-type mice. These events were correlated with an increase in the staining (immunoreactivity) for poly (ADP-ribose) polymerase (PARP) in the pancreas of cerulein-treated IL-6WT. The staining for PARP was more pronounced in IL-6KO mice subjected to acute pancreatitis than in the corresponding WT mice. These data demonstrate that endogenous IL-6 exerts an anti-inflammatory role during acute pancreatitis, possibly by regulating the expression of adhesion molecules, the subsequent adhesion and activation of neutrophils and finally the generation of cytokine and reactive oxygen or nitrogen species. (C) 2002 Published by Elsevier Science Ltd.
引用
收藏
页码:274 / 285
页数:12
相关论文
共 58 条
[1]   Interleukin 6 is required for the development of collagen-induced arthritis [J].
Alonzi, T ;
Fattori, E ;
Lazzaro, D ;
Costa, P ;
Probert, L ;
Kollias, G ;
De Benedetti, F ;
Poli, V ;
Ciliberto, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (04) :461-468
[2]   Impaired Stat3 activation following localized inflammatory stimulus in IL-6-deficient mice [J].
Alonzi, T ;
Fattori, E ;
Cappelletti, M ;
Ciliberto, G ;
Poli, V .
CYTOKINE, 1998, 10 (01) :13-18
[3]  
*AM COLL CHEST PHY, 1993, CRIT CARE MED, V20, P864
[4]   PROTECTIVE ROLE OF INTERLEUKIN-6 IN THE LIPOPOLYSACCHARIDE-GALACTOSAMINE SEPTIC SHOCK MODEL [J].
BARTON, BE ;
JACKSON, JV .
INFECTION AND IMMUNITY, 1993, 61 (04) :1496-1499
[5]   BACTERIAL-CONTAMINATION OF PANCREATIC NECROSIS - A PROSPECTIVE CLINICAL-STUDY [J].
BEGER, HG ;
BITTNER, R ;
BLOCK, S ;
BUCHLER, M .
GASTROENTEROLOGY, 1986, 91 (02) :433-438
[6]   PASSIVE-IMMUNIZATION AGAINST CACHECTIN TUMOR NECROSIS FACTOR PROTECTS MICE FROM LETHAL EFFECT OF ENDOTOXIN [J].
BEUTLER, B ;
MILSARK, IW ;
CERAMI, AC .
SCIENCE, 1985, 229 (4716) :869-871
[7]   Interleukin-6 in the injured patient marker of injury or mediator of inflammation? [J].
Biffl, WL ;
Moore, EE ;
Moore, FA ;
Peterson, VM .
ANNALS OF SURGERY, 1996, 224 (05) :647-664
[8]  
BRADLEY EL, 1993, ARCH SURG-CHICAGO, V128, P586
[9]   Interleukin-6 is required for a protective immune response to systemic Escherichia coli infection [J].
Dalrymple, SA ;
Slattery, R ;
Aud, DM ;
Krishna, M ;
Lucian, LA ;
Murray, R .
INFECTION AND IMMUNITY, 1996, 64 (08) :3231-3235
[10]   N-acetylcysteine decreases severity of acute pancreatitis in mice [J].
Demols, A ;
Van Laethem, JL ;
Quertinmont, E ;
Legros, F ;
Louis, H ;
Le Moine, O ;
Devière, J .
PANCREAS, 2000, 20 (02) :161-169