AJP - Gastrointestinal and Liver Physiology, Vol 271, Issue 6 980-G986, Copyright © 1996 by American Physiological Society
Tumor necrosis factor unresponsiveness after surgery in bile duct-ligated rats
A. P. Houdijk, M. A. Boermeester, R. I. Wesdorp, C. E. Hack and P. A. Van Leeuwen
Department of Surgery, Free University Hospital, Central Laboratory of The Netherlands, Red Cross Blood Transfusion Service, Amsterdam, The Netherlands.
In obstructive jaundice, postoperative complications are related to
gut-derived endotoxemia and possibly mediated by cytokines such as tumor
necrosis factor (TNF) and interleukin-6 (IL-6). This study investigated the
course of IL-6 and TNF after 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. Surgery elicited a
significant IL-6 response in saline-treated BDL rats (BDL-SAL). TNF,
however, remained at its low preoperative levels. Cholestyramine treatment
resulted in undetectable preoperative TNF and IL-6 levels, but levels of
both cytokines were significantly raised after surgery. Endotoxin, as
determined by the CD14 blockade test, was identified in the BDL-SAL group,
before (time 0) and after surgery (2 and 4 h), whereas in the
cholestyramine group endotoxin was only present at 2 h after 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.
