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Systemic and Local Inflammatory Mediator Response to Major Surgery

Author

Summary, in English

Cell-signalling via cytokines modulates the local response to surgical trauma, directs the immunologic response and initiates the healing process. Surgical trauma induces a systemic cytokine response and a down-regulation of the antigen presentation capacity of monocytes (HLA-DR expression), which is associated with a poor prognosis if pronounced. The aims with the studies in this thesis were to identify factors that modulate the cytokine and the immune-cell responses to major surgery and to evaluate the role of collagenases in colonic healing.



Major surgery evoked a cytokine response in the systemic circulation, which was enhanced by the presence of a cancer, in colorectal resections. The IL-6 response in colorectal surgery originated from the bowel and enhanced concentrations of IL-6 in tissue of colorectal cancers, emanating from an IL-6 expression in the malignant epithelium, might be the source. Open surgery for abdominal aortic aneurysm (AAA) repair induced higher IL-6 responses than transfemorally placement of endoluminal grafts (TPEG), lower peri-operative sigmoidal pH but equal down-regulation of the HLA-DR expression on monocytes. These findings suggest that tissue destruction influences the systemic IL-6 response in trauma, but not the down-regulation HLA-DR expression on monocytes.



Experimental colonic obstruction in rats implied a local inflammatory response and an increased break-down of collagen by matrix metalloproteinases in the colonic wall, leading to a decrease in collagen concentration, assessed as hydroxyproline concentration. Inhibition of MMPs in the early phase of anastomotic healing in the colon, resulted in increased breaking strength of the anastomoses in inhibitor-treated animals compared to controls, confirming a negative role of MMPs in this phase of colonic healing. The knowledge on cytokine response to surgical trauma and interactions with the healing process needs to be expanded by studies on local events in tissue. The information on collagenase up-regulation in the local inflammatory response in the colon and the results of MMP-inhibition in anastomotic healing are promising in the efforts to improve healing in colorectal surgery.

Department/s

Publishing year

2000

Language

English

Document type

Dissertation

Publisher

Department of Surgery, Malmö University Hospital, Lund University

Topic

  • Surgery

Keywords

  • orthopaedics
  • Surgery
  • traumatologi
  • ortopedi
  • Kirurgi
  • traumatology

Status

Published

Research group

  • Surgery

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-4355-9
  • ISRN: LUMEDW/MESM-1078-SE

Defence date

29 November 2000

Defence time

10:15

Defence place

Dept of Surgery, Malmö University Hospital, Entrance 42, Lecture Hall, Ground floor

Opponent

  • Ulf Haglund