Abstract
Acute appendicitis is a common surgical emergency worldwide. Exaggerated immune responses could be associated with appendicitis. This study aimed at characterizing immune responses towards a large variety of gut commensals and pathogens, and pattern recognition receptor (PRR) ligands, and investigating the course of systemic inflammation in a prospective cohort of acute appendicitis patients. PBMC responses of 23 patients of the cohort and 23 healthy controls were characterized more than 8 months post-surgery. Serum cytokine levels were measured in 23 patients at the time of appendicitis and after one month. CRP, WBC and percentage of neutrophils were analyzed in the total cohort of 325 patients. No differences in PBMC responses were found between patients and controls. Stronger IL-10 responses were found following complicated appendicitis. A trend towards lower IL-8 responses was shown following gangrenous appendicitis. Serum IL-10 and IL-6 were significantly elevated at presentation, and IL-6, IL-8 and TNF-α levels were higher in complicated appendicitis. Routine biomarkers could predict severity of appendicitis with high specificities, but low sensitivities. Cytokine responses in patients following acute appendicitis did not differ from healthy controls. Higher serum cytokine levels were found in acute complicated and gangrenous cases. Further research into discriminative biomarkers is warranted.
Highlights
Shifted towards the microbiome as a whole
After stimulation of peripheral blood mononuclear cells (PBMC) with tetanus toxoid, an increase of secretion of interferon gamma (IFN-γ) in patients with gangrenous appendicitis compared to negative appendectomy controls has been observed, and interleukin (IL)-10 secretion after stimulation is increased in gangrenous compared to phlegmonous appendicitis patients[11]
There was an equal number of patients with complicated appendicitis according to International Classification of Diseases (ICD)-9 and gangrenous appendicitis (n = 7), yet only three cases were classified as both complicated and gangrenous
Summary
Shifted towards the microbiome as a whole. The composition of microbiota in the appendix differs from other regions in the gastrointestinal tract[8], and there is large variation between individuals. High IL-8 levels can be observed in the appendix, the peritoneal fluid, and according to some studies in the serum of p atients[12]. IL-6 can be considered as a biomarker for appendicitis as well, since high serum levels can often be associated with the condition[17]. High grade inflammation and tissue damage appear to be a mechanism in the development of appendicitis, possibly caused by deviant immune responses. We hypothesized that the risk of appendicitis and the severity of inflammation are dependent on the individual’s innate immune responses towards components of the gut microbiota. The main aim of this study was to characterize potential deviant immune responses to stimulation by a large panel of gut bacteria, other commensals and relevant corresponding Pattern Recognition Receptor (PRR) ligands
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