TY - JOUR
T1 - Induction of IL-6 within the rodent intestinal muscularis after intestinal surgical stress
AU - Wehner, Sven
AU - Schwarz, Nicolas T.
AU - Hundsdoerfer, Ricarda
AU - Hierholzer, Christian
AU - Tweardy, David J.
AU - Billiar, Timothy R.
AU - Bauer, Anthony J.
AU - Kalff, Joerg C.
PY - 2005/4
Y1 - 2005/4
N2 - Background. Postoperative ileus is a poorly understood surgical problem characterized by leukocyte extravasation into the intestinal muscularis and suppression in muscle function. The study objective was to delineate a mechanistic inflammatory cascade initiated by intestinal manipulation. Methods. ACI and Sprague-Dawley rats, and IL-6+/+ and IL-6-/- mice were subjected to intestinal manipulation. One group of rats received adhesion molecule-blocking antibodies (1A29 and WT.3) before intestinal manipulation. Interleukin-6 (IL-6) messenger RNA (mRNA) levels and electrophoretic mobility shift assay for signal transducers and activators of transcription (STAT) activation were measured in tissue extracts. IL-6 protein levels were assessed by immunohistochemistry and enzyme-linked immunosorbent assay. Results. IL-6 mRNA from muscularis extracts demonstrated a significant induction after intestinal manipulation. No IL-6 induction was observed in mucosal extracts. Adhesion molecule blockade resulted in a marked decrease of cellular infiltration but did not change IL-6 mRNA expression in muscularis extracts. Resident macrophages in the muscularis stained for IL-6 by immunohistochemistry after intestinal manipulation. The isolated manipulated muscularis demonstrated a significant increase in IL-6 release. Electrophoretic mobility shift assay of manipulated muscularis showed a marked increase in IL-6-dependent Stat3 activation. Conclusions. This study demonstrates that manipulation of the small bowel during an abdominal operation initiates downstream induction, translation, release, and functional activity of IL-6 within the muscularis.
AB - Background. Postoperative ileus is a poorly understood surgical problem characterized by leukocyte extravasation into the intestinal muscularis and suppression in muscle function. The study objective was to delineate a mechanistic inflammatory cascade initiated by intestinal manipulation. Methods. ACI and Sprague-Dawley rats, and IL-6+/+ and IL-6-/- mice were subjected to intestinal manipulation. One group of rats received adhesion molecule-blocking antibodies (1A29 and WT.3) before intestinal manipulation. Interleukin-6 (IL-6) messenger RNA (mRNA) levels and electrophoretic mobility shift assay for signal transducers and activators of transcription (STAT) activation were measured in tissue extracts. IL-6 protein levels were assessed by immunohistochemistry and enzyme-linked immunosorbent assay. Results. IL-6 mRNA from muscularis extracts demonstrated a significant induction after intestinal manipulation. No IL-6 induction was observed in mucosal extracts. Adhesion molecule blockade resulted in a marked decrease of cellular infiltration but did not change IL-6 mRNA expression in muscularis extracts. Resident macrophages in the muscularis stained for IL-6 by immunohistochemistry after intestinal manipulation. The isolated manipulated muscularis demonstrated a significant increase in IL-6 release. Electrophoretic mobility shift assay of manipulated muscularis showed a marked increase in IL-6-dependent Stat3 activation. Conclusions. This study demonstrates that manipulation of the small bowel during an abdominal operation initiates downstream induction, translation, release, and functional activity of IL-6 within the muscularis.
UR - http://www.scopus.com/inward/record.url?scp=15944424351&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2004.11.003
DO - 10.1016/j.surg.2004.11.003
M3 - Article
C2 - 15800492
AN - SCOPUS:15944424351
SN - 0039-6060
VL - 137
SP - 436
EP - 446
JO - Surgery
JF - Surgery
IS - 4
ER -