Induction of IL-6 within the rodent intestinal muscularis after intestinal surgical stress.
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.
Wehner
Sven
S
Department of Surgery, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Schwarz
Nicolas T
NT
Hundsdoerfer
Ricarda
R
Hierholzer
Christian
C
Tweardy
David J
DJ
Billiar
Timothy R
TR
Bauer
Anthony J
AJ
Kalff
Joerg C
JC
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007421:Intestine, Small / Q000276:immunology* / Q000601:surgery*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D023421:Models, Animal; D009130:Muscle, Smooth / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011912:Rats, Inbred ACI; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D015850:Interleukin-6; D012333:RNA, Messenger