liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Systemic Th17-like cytokine pattern in gangrenous appendicitis but not in phlegmonous appendicitis
Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
County Hospital Ryhov.
Karolinska University Hospital.
University of Copenhagen.
Show others and affiliations
2010 (English)In: SURGERY, ISSN 0039-6060, Vol. 147, no 3, 366-372 p.Article in journal (Refereed) Published
Abstract [en]

Background. Increasing circumstantial evidence suggests that not all patients with appendicitis will progress to perforation and that appendicitis that resolves may be a common event. Based on this theory and on indications of aberrant regulation of inflammation in gangrenous appendicitis, we hypothesized that. phlegmonous and gangrenous appendicitis are different entities with divergent immunoregulation. Methods. Blood samples were collected from patients with gangrenous appendicitis (n = 16), phlegmonous appendicitis (n = 21), and nonspecific abdominal pain (n = 42). Using multiplex bead arrays, we analyzed a range of inflammatory markers, such as interleukin (IL)-1ra, IL-1r beta, IL-2 IL-6, IL-10, IL-12p70, IL-15, and IL-17; interferon-gamma; tumor necrosis factor; CXCL8; CCL2; CCL3; and matrix metalloproteinase (MMP)-1 MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MMP-13 in blood. Results. Compared with patients with phlegmonous appendicitis and nonspecific abdominal pain, the patients With gangrenous appendicitis had increased levels of the proinflammatory markers IL-6, CCL2, IL-17, MMP-8, and MMP-9 (P andlt;= .04 each) accompanied by increased levels of the anti-inflammatory cytokines IL-1ra and IL-10 (P andlt;= .02). Patients with phlegmonous appendicitis had increased levels of IL-10 only. Conclusion. The finding of a pattern inflammatory markers compatible with the highly inflammatory A 17 subset in sera from, patients with gangrenous appendicitis, but not in phlegmonous appendicitis, supports the hypothesis that gangrenous and phlegmonous appendicitis are different entities with diver gent immune regulation. Additional studies of the differential immunopathogenesis of phlegmonous and gangrenous appendicitis are warranted, as this may have important implications in the diagnosis and management of patients with suspicion of appendicitis.

Place, publisher, year, edition, pages
2010. Vol. 147, no 3, 366-372 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-54601DOI: 10.1016/j.surg.2009.09.039ISI: 000275350700007OAI: oai:DiVA.org:liu-54601DiVA: diva2:305999
Available from: 2010-03-26 Created: 2010-03-26 Last updated: 2013-08-29
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

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Rubér, MarieAndersson, RolandEkerfelt, Christina

Search in DiVA

By author/editor
Rubér, MarieAndersson, RolandEkerfelt, Christina
By organisation
SurgeryFaculty of Health SciencesClinical Immunology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 180 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf