Tumor necrosis factor unresponsiveness after surgery in bile duct
ligated rats.
Houdijk, A. P. J., M. A. Boermeester, R. I. C. Wesdorp, C. Erik Hack,
and P. A. M. Van Leeuwen.
Departments of Surgery and Internal Medicine, Free University
Hospital: Central Laboratory of the Netherlands Red Cross Blood
Transfusion Service and Laboratory for Experimental and Clinical
Immunology, University of Amsterdam, Amsterdam, the Netherlands
APStracts 3:0116G, 1996.
In obstructive jaundice postoperative complications are related to gut
derived endotoxemia and possibly mediated by cytokines like TNF and
IL-6. This study investigated the course of IL-6 and TNF following
surgery in bile duct ligated rats (BDL) treated with and without an
enteral endotoxin binder (cholestyramine). Endotoxin in rat plasma
was determined by blocking cytokine production in whole blood cell
cultures stimulated by rat plasma using antibodies directed against
the endotoxin (CD14) receptor. Results showed that in saline treated
BDL rats (BDL-SAL) surgery elicited a significant IL-6 response. TNF
however remained at its low preoperative levels. Cholestyramine
treatment resulted in undetectable preoperative TNF and IL-6 levels
but both cytokines were significantly raised after surgery.
Endotoxin, as determined by the CD14 blockade test, was identified in
the BDL-SAL group before (t=0 hrs) and after surgery (t=2 and 4 hrs)
whereas in the cholestyramine group endotoxin was only present at t=2
hrs following surgery. The lack of a postoperative plasma TNF
response in the BDL-SAL group, in the continuous presence of
endotoxin, suggests endotoxin tolerance for TNF production in
obstructive jaundice.
Received 10 January 1996; accepted in final form 28 May 1996.
APS Manuscript Number G12-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96