Experimental acute pancreatitis results in increased blood-brain barrier permeability in the rat: a potential role for tumor necrosis factor and interleukin 6.
Pancreatic encephalopathy is a severe complication of acute pancreatitis. Proinflammatory cytokines may play a role in the development of multi-organ failure during pancreatitis. In the present study, we measured the changes in the blood-brain barrier (BBB) permeability concomitantly with the determination of serum tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in rats before, as well as 6, 24 and 48 h after the beginning of intraductal taurocholic acid-induced acute pancreatitis. Cytokine concentrations were measured in bioassays with specific cell lines (WEHI-164 for TNF and B-9 for IL-6), while the BBB permeability was determined for a small (sodium fluorescein, molecular weight (MW) 376 Da), and a large (Evans' blue-albumin, MW 67000 Da) tracer by spectrophotometry in the parietal cortex, hippocampus, striatum, cerebellum and medulla of rats. The serum TNF level was significantly (P < 0.05) increased 6 and 24 h after the induction of pancreatitis, while the IL-6 level increased after 24 and 48 h. A significant (P < 0.05) increase in BBB permeability for both tracers developed at 6 and 24 h in different brain regions of animals with acute pancreatitis. We conclude that cytokines, such as TNF and IL-6, may contribute to the vasogenic brain edema formation during acute pancreatitis.
Farkas
G
G
Department of Surgery, Albert Szent-Györgyi University Medical School, Szeged, Hungary. farkas@surg.szote.u-szeged.hu
Márton
J
J
Nagy
Z
Z
Mándi
Y
Y
Takács
T
T
Deli
M A
MA
Abrahám
C S
CS
D000681:Amylases / Q000097:blood; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D001929:Brain Edema / Q000503:physiopathology; D002756:Cholagogues and Choleretics; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000503:physiopathology; D005070:Evans Blue / Q000493:pharmacokinetics; D019793:Fluorescein / Q000493:pharmacokinetics*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D002756:Cholagogues and Choleretics; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005070:Evans Blue; D013656:Taurocholic Acid; D000681:Amylases; D019793:Fluorescein