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- Rubér, Marie, et al.
(författare)
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Dysregulated Th1/Th17 response in advanced appendicitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The pathogenesis of appendicitis, the most common abdominal emergency for surgical intervention, is still unknown. Epidemiological differences between perforated and nonperforated appendicitis, polymorphism in the interleukin (IL)-6 gene associated with severity of appendicitis and a more pronounced Th1/Th17-like deviation in advanced compared to phlegmonous appendicitis has been reported. Altogether these findings may indicate that appendicitis harbours two different entities with different immuno-pathogenesis, one progressing to gangrene and perforation and one resolving. In this study we aimed to further investigate systemic cytokine profiles in a large sample of patients, with advanced and phlegmonous appendicitis from a Th1, Th2, Th17 and innate perspective, and also clarify if time as duration of symptoms could explain the differences.Methods: Blood samples were preoperatively collected from patients with advanced (n=61) and phlegmonous appendicitis (n=108). The Th1-associated (IFN-γ, IL-12p70), Th2-associated (IL-4, IL-5), Th17-associated (IL-17, IL-6, CCL20, CCL2) and innate-associated (IL-1β, IL-6, MPO, CXCL8, GM-CSF), markers were analyzed in plasma using multiplex bead assay.Results: Patients with advanced appendicitis had increased levels of IL-6 (P=0.0001), CCL2 (P=0.001), MPO (P=0.039), IL-12p70 (P=0.010) and CCL20 (P=0.002) as compared to phlegmonous appendicitis and age, sex or duration of symptoms at sampling could not explain the differences.Conclusion: The findings suggest a dysregulated Th1/Th17 type inflammation in advanced appendicitis, already early in the disease course, that eventuates in gangrene and perforation and gives further support to the notion of appendicitis as two entities.
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| 2. |
- Rubér, Marie, et al.
(författare)
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Local and systemic cytokine secretion in advanced and phlegmonous appendicitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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