Abstract | OBJECTIVE: To investigate the initiation of a complex inflammatory response within the human intestinal muscularis intraoperatively so as to determine the clinical applicability of the inflammatory hypothesis of postoperative ileus. SUMMARY BACKGROUND DATA: Mild intestinal manipulation in rodents initiates the activation of transcription factors, upregulates proinflammatory cytokines, and increases the release of kinetically active mediators ( nitric oxide and prostaglandins), all of which results in the recruitment of leukocytes and a suppression in motility (i.e., postoperative ileus). METHODS: RESULTS: Normal human muscularis externa contained numerous macrophages that expressed increased lymphocyte function associated antigen-1 (LFA-1) immunoreactivity as a function of intraoperative time. RT-PCR demonstrated a time-dependent induction of IL-6, IL-1beta, TNF-alpha, iNOS, and COX-2 mRNAs within muscularis extracts after incision. Mediators were localized to macrophages with STAT protein activation in protein extracts demonstrating local IL-6 functional activity. DFU alone or in combination with GW274150C increased circular muscle contractility. Specimens harvested after reoperation developed leukocytic infiltrates and displayed diminished in vitro muscle contractility. CONCLUSIONS: These human data demonstrate that surgical trauma is followed by resident muscularis macrophage activation and the upregulation, release, and functional activity of proinflammatory cytokines and kinetically active mediators.
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Authors | Jörg C Kalff, Andreas Türler, Nicolas T Schwarz, Wolfgang H Schraut, Kenneth K W Lee, David J Tweardy, Timothy R Billiar, Richard L Simmons, Anthony J Bauer |
Journal | Annals of surgery
(Ann Surg)
Vol. 237
Issue 3
Pg. 301-15
(Mar 2003)
ISSN: 0003-4932 [Print] United States |
PMID | 12616113
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Acute-Phase Proteins
- Cytokines
- DNA-Binding Proteins
- Inflammation Mediators
- Interleukin-1
- Isoenzymes
- Membrane Proteins
- STAT3 Transcription Factor
- STAT3 protein, human
- Trans-Activators
- Tumor Necrosis Factor-alpha
- NOS2 protein, human
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Cyclooxygenase 2
- PTGS2 protein, human
- Prostaglandin-Endoperoxide Synthases
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Topics |
- Acute-Phase Proteins
(metabolism)
- Cyclooxygenase 2
- Cytokines
(metabolism)
- DNA-Binding Proteins
(metabolism)
- Electrophoretic Mobility Shift Assay
- Humans
- Immunohistochemistry
- In Vitro Techniques
- Inflammation Mediators
(metabolism)
- Interleukin-1
(metabolism)
- Isoenzymes
(metabolism)
- Jejunum
(cytology, immunology, metabolism, surgery)
- Laparotomy
- Macrophage Activation
- Macrophages
(cytology)
- Membrane Proteins
- Muscle Contraction
- Muscle, Smooth
(immunology, metabolism, physiopathology)
- Nitric Oxide Synthase
(metabolism)
- Nitric Oxide Synthase Type II
- Polymerase Chain Reaction
- Prostaglandin-Endoperoxide Synthases
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- STAT3 Transcription Factor
- Signal Transduction
- Trans-Activators
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
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