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Local and systemic cytokine secretion in advanced and phlegmonous appendicitis
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
Unit for Autoimmunity and Immune regulation, County hospital Ryhov, Jönköping, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
Copenhagen University, Faculty of Health Sciences, Department of Surgery, Hospital Nord, Holbæk, Denmark.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Appendicitis is the most common abdominal emergency for surgery, but its underlying pathogenesis is still unknown. Appendicitis most likely harbors two different entities with different pathogenesis, one progressing to gangrene and perforation and one resolving. Previous studies on cytokines in peripheral blood points to different immunopathogenesis in advanced and resolving appendicitis. The relation of the peripheral blood analyzes to the local immune response in appendix is unclear. This study investigated local immune response in the appendix compared to blood, utilizing enzyme linked immunospot essay (ELISpot) which allows detection of low grade cytokine secretion from single cells.

Methods: Appendiceal tissue and blood samples were collected from patients with advanced (gangrenous or perforated) (n=11) and phlegmonous appendicitis (n=7). Mononuclear cells were analyzed with ELISpot for number of spontaneous and PHA stimulated IFN-γ-, IL-12p70-(both Th1), IL-4-(Th2), IL-17-(Th17), TGF-β-(anti-inflammatory/Th17) and IL-10-(anti-inflammatory/Th1) secreting cells.

Results: In appendix, the number of IL-4-(P=0.042) and IL-10-(P=0.042) secreting cells was increased in advanced appendicitis as compared to phlegmonous and a trend for increase was observed for IL-12p70 (P=0.055) and TGF-β (P=0.067). In blood the number of IL-4-(P=0.045), TGF-β-(P=0.007) and IFN-γ-(P=0.019), secreting cells were increased in patients with advanced appendicitis and a trend for increase was observed for IL-12p70 (P=0.068)

Conclusion: Present findings are in line with previous studies demonstrating an increased inflammatory response in advanced as compared to phlegmonous appendicitis. The local immune response in the appendiceal tissue is mirrored in the blood, which justifies the use of analyzes on peripheral blood when investigating immune response in appendicitis.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-80374OAI: oai:DiVA.org:liu-80374DiVA: diva2:546643
Available from: 2012-08-24 Created: 2012-08-24 Last updated: 2012-08-24Bibliographically approved
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)
Opponent
Supervisors
Available from: 2012-08-24 Created: 2012-08-24 Last updated: 2013-08-29Bibliographically approved

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Rubér, MarieAndersson, Roland E

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