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Different cytokine profiles in patients with a history of gangrenous or phlegmonous appendicitis
Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.ORCID iD: 0000-0002-3993-9985
Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
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2006 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 143, no 1, 117-124 p.Article in journal (Refereed) Published
Abstract [en]

Appendicitis is one of the most common and costly acute abdominal states of illnesses. Previous studies suggest two types of appendicitis which may be different entities, one which may resolve spontaneously and another that progresses to gangrene and perforation. Gangrenous appendicitis has a positive association to states of Th1 mediated immunity whereas Th2 associated immune states are associated with lower risk of appendicitis. This study investigated the inflammatory response pattern in patients previously appendicectomized for gangrenous (n = 7), or phlegmonous appendicitis (n = 8) and those with a non-inflamed appendix (n = 5). Peripheral blood mononuclear cells were analysed with ELISPOT analysis for number of spontaneous or antigen/mitogen stimulated IFN-γ, IL-4, IL-10 and IL-12 secreting cells or with ELISA for concentration of spontaneous or antigen/mitogen stimulated IFN-γ, IL-5 and IL-10. Spontaneously IL-10 secreting cells/100 000 lymphocytes were increased in the gangrenous group compared to the phlegmonous group (P = 0.015). The median concentration of IL-10 secreted after Tetanus toxoid (TT)-stimulation were higher in the gangrenous group and the control group, than the phlegmonous group (P = 0.048 and P = 0.027, respectively). The median concentration of TT induced IFN-γ secretion was higher for the gangrenous group compared to both the phlegmonous group and the control group (P = 0.037 and P = 0.003). Individuals with a history of gangrenous appendicitis demonstrated ability to increased IL-10 and IFN-γ production. The increased IFN-γ may support the notion of gangrenous appendicitis as an uncontrolled Th1 mediated inflammatory response and increased IL-10 may speculatively indicate the involvement of cytotoxic cells in the progression to perforation. © 2005 British Society for Immunology.

Place, publisher, year, edition, pages
2006. Vol. 143, no 1, 117-124 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-37618DOI: 10.1111/j.1365-2249.2005.02957.xLocal ID: 36747OAI: oai:DiVA.org:liu-37618DiVA: diva2:258467
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
In thesis
1. Immunopathogenic aspects of resolving and progressing appendicitis
Open this publication in new window or tab >>Immunopathogenic aspects of resolving and progressing appendicitis
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Appendicitis is one of the most common diseases requiringemergency surgical intervention. There are several indications that the diagnosisappendicitis harbours two different entities, one progressing to gangrene and perforation(advanced) and one that resolves spontaneously (phlegmonous). An immunologically drivenpathogenesis in appendicitis has been suggested on the basis of an inverse relationshipbetween appendicitis and ulcerative colitis, a positive association with Crohn’s disease, anda decreased incidence during pregnancy, generating the hypothesis that theimmunopathogenesis in advanced appendicitis is characterized by a Th1 inflammatoryresponse. The aim of this thesis was to test this hypothesis and investigate the immuneresponse in advanced and phlegmonous appendicitis.

Material and Methods: The immunologic response was investigated in appendicitis tissue and compared to the immunological response in peripheral blood, analysed by enzyme-linked immunospot assay (ELISPOT). The response pattern was also investigated in patients with an actual appendicitis in the peripheral plasma and peripheral serum before surgery, analysed with Luminex. The immunological response pattern was investigated in peripheral blood several months to years after an appendectomy using ELISPOT and enzyme-linked immunosorbent assay (ELISA).

Results: The local immune response in the appendiceal tissue in appendicitis was similar to the response in peripheral blood. Patients with actual advanced appendicitis had increased levels of IL-6, CCL20, CCL2, TGF-β, IL-17, IFN-γ, IL-12p70, IL-10, IL-1ra, IL-4, MMP-8, MMP-9 and MPO compared with those with phlegmonous appendicitis. Sex, age or duration of symptoms could not explain the differences between the groups. Individuals with a history of advanced appendicitis had increased secretion of IFN-γ months to years after the appendectomy compared with individuals with a history of phlegmonous appendicitis.

Conclusions: The local immune response in the appendiceal tissue is mirrored in the blood, which justifies the use of peripheral blood in studies on appendicitis. The immunological response pattern in peripheral blood suggests Th1/Th17- induced inflammation in advanced appendicitis that is present at an early stage. Individuals with a history of advanced appendicitis have stronger Th1 responses than individuals with a history of phlegmonous appendicitis. This may reflect constitutional differences between patients with different outcomes of appendicitis. The increased inflammatory response observed early in advanced appendicitis suggests a more violent inflammation and supports the hypothesis of different immune pathogeneses, where excessive induction of Th1/Th17 immunity and/or deficiencies in down-regulatory feedback mechanisms may explain the excessive inflammation in advanced appendicitis, where the inflammation eventuates in gangrene and perforation.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 89 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1314
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-80375 (URN)978-91-7519-855-2 (ISBN)
Public defence
2012-09-14, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
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Available from: 2012-08-24 Created: 2012-08-24 Last updated: 2013-08-29Bibliographically approved

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Rubér, MarieEkerfelt, ChristinaOlaison, GunnarAndersson, Roland

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Faculty of Health SciencesDivision of surgeryClinical ImmunologyDepartment of Surgery in Östergötland
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