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Inflammatory Reactions in Peritonitis and Malignant Obstructive Jaundice: Clinical and Experimental Studies with Special Emphasis on the Cellular Immune Response
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with peritonitis or malignant obstructive jaundice (HPB+) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-α and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-α level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs.

BT occurred infrequently in patients with acute peritonitis and in HPB+ there was no evidence of BT. Peritonitis and HPB+ causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB+ a high rate of apoptosis in MLNs was observed.

An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB+. Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2005. , p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 3
Keyword [en]
Surgery, CLP, sepsis, peritonitis, bacterial translocation, malignant obstructive jaundice, Linomide, COX inhibitor, SC-236, indometacin, T lymphocyte, macrophage, mucosa, MLN, gut immune cell distribution, mucosal injury, cytokines, TNF-α, IL-6, IL-10, endotoxin, caspase-3, apoptosis
Keyword [sv]
Kirurgi
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-4767ISBN: 91-554-6138-7 (print)OAI: oai:DiVA.org:uu-4767DiVA, id: diva2:165684
Public defence
2005-03-11, Auditorium Minor, Gustavianum, Akademigatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved
List of papers
1. Alteration in mucosal immune cell distribution in septic rats
Open this publication in new window or tab >>Alteration in mucosal immune cell distribution in septic rats
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1997 In: Shock, ISSN 1073-2322, Vol. 7, no 3, p. 182-185.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92553 (URN)
Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved
2. Effect of Linomide on gut immune cell distribution and on TNF-α in plasma and ascites:an experimental study in the septic rat
Open this publication in new window or tab >>Effect of Linomide on gut immune cell distribution and on TNF-α in plasma and ascites:an experimental study in the septic rat
2002 In: Shock, ISSN 1073-2322, Vol. 18, no 5, p. 471-475Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92554 (URN)
Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved
3. Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis
Open this publication in new window or tab >>Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-92555 (URN)
Available from: 2005-02-17 Created: 2005-02-17 Last updated: 2010-01-13Bibliographically approved
4. Microbial translocation and inflammatory response in patients with acute peritonitis
Open this publication in new window or tab >>Microbial translocation and inflammatory response in patients with acute peritonitis
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2004 In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 39, no 7, p. 657-664Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-92556 (URN)
Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved
5. Inflammatory response in patients with malignant obstructive jaundice
Open this publication in new window or tab >>Inflammatory response in patients with malignant obstructive jaundice
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2007 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 1, p. 94-102Article in journal (Refereed) Published
Abstract [en]

Objective. Surgery in patients with malignant obstructive jaundice is associated with increased risks for postoperative septic complications. The aim of this study was to investigate the inflammatory and the local cellular immune response in patients accepted for surgery because of tumours in the hepatic-pancreatic-biliary (HPB) tract. Material and methods. Patients with obstructive jaundice (group HPB+) were compared with those without (HPB-). Patients undergoing surgery for benign abdominal disorders served as controls. Obstructive jaundice was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for bacteria, endotoxins and cytokines (TNF-α, IL-6 and IL-10). At operation, mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard microbiological techniques, and immunohistochemistry, using antibodies CD4 and CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to determine the rate of apoptosis). Results. Bacterial translocation was not demonstrated in any of the patients. Increased preoperative concentrations of endotoxins were found in group HPB+. The number of macrophages and the rate of apoptosis in MLNs were increased in jaundiced patients, while the number of T lymphocytes was decreased. Conclusions. Malignant obstructive jaundice causes increased blood concentrations of endotoxins and cytokines, an increased number of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the increased rate of apoptosis, and might reduce the ability of jaundiced patients to eradicate infection.

Keyword
Apoptosis, bacterial translocation, cytokines, endotoxins, lymphocytes, obstructive jaundice, surgery
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-92557 (URN)10.1080/00365520600825190 (DOI)000243724800016 ()17190769 (PubMedID)
Available from: 2005-02-17 Created: 2005-02-17 Last updated: 2017-12-14Bibliographically approved

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