Anti-tumor necrosis factor antibody augments edema formation in caerulein-induced acute pancreatitis.
The pathogenesis of acute pancreatitis is incompletely defined, but the outcome is determined in part by an acute inflammatory process. Pancreatitis-associated inflammation appears to play a role in the local retroperitoneal injury as well as in the associated dysfunction of remote organs such as the lung. Tumor necrosis factor (TNF) appears to be a proximal mediator of the inflammatory response. In this study, anti-TNF antibody was administered to rats with caerulein-induced pancreatitis to determine if the observed increases in pancreatic and pulmonary microvascular permeability were related to plasma TNF activity. In contrast to the expected findings, blockade of TNF activity was found to increase the amount of edema formation in both the pulmonary and pancreatic microvascular beds. The mechanism is not known; however, blockade of TNF-induced down regulation of phagocytic cell activity, ablation of TNF-dependent feedback inhibition of other cytokines, failure of induction of endogenous antioxidant systems, or inactivation of the TNF control of microvascular tone are all possible explanations. This is potentially an important observation as clinical strategies are now being developed to modify the inflammatory response in ways presumed advantageous to an injured host.
Guice
K S
KS
Section of General Surgery, University of Michigan School of Medicine, Ann Arbor 48109.
Oldham
K T
KT
Remick
D G
DG
Kunkel
S L
SL
Ward
P A
PA
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000502:physiology*; D002108:Ceruletide; D004487:Edema / Q000209:etiology / Q000276:immunology*; D008297:Male; D010182:Pancreatic Diseases / Q000209:etiology / Q000276:immunology*; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000276:immunology*; D011654:Pulmonary Edema / Q000209:etiology / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide