A Th2 Cytokine Profile in Appendicular Lavage Fluid Suggests Allergy as a Possible Etiology for Acute Appendicitis

Abstract

Acute appendicitis is the most frequent surgical abdominal emergency, but its etiology remains poorly understood. Histological examination of the appendix, following its removal due to acute appendicitis, consistently shows features in common with bronchial asthma, suggesting an allergic reaction as a candidate etiologic factor. Here, we propose the concept of appendicular lavage and use it to study the levels of the Th2 cytokines IL-4, IL-5, and IL-9 in patients with a clinical diagnosis of acute appendicitis. The study group included 20 patients with a histological diagnosis of phlegmonous appendicitis, 13 patients with gangrenous appendicitis, and a control group of 8 patients with a clinical diagnosis of appendicitis but with normal histology. Cytokine levels were higher in acute appendicitis. The difference was more pronounced when comparing phlegmonous appendicitis with nonpathological appendicitis (p = 0.01) for IL-4 (48.3 vs. 21.3 pg/mL), IL-5 (29.2 vs. 8.0 pg/mL), and IL-9 (34.1 vs. 16.6 pg/mL). This Th2 cytokine profile is compatible with the hypothesis of allergy as an etiologic factor for acute appendicitis and may have important implications for the diagnosis, prevention, and treatment of this condition.

An Evaluation of Serum IgE and Th2-Associated Interleukins in Children With Uncomplicated and Complicated Appendicitis

“…The hypothesis that cytokines reflect different types of inflammatory responses (Th1/Th17, Th2) which could be used as biomarkers in patients with appendicitis has also been proposed. In a previous study investigating concentrations of Th2 cytokines in appendicular lavage in 41 adults, concentrations of IL-4 were significantly higher in the patients with phlegmonous appendicitis compared to those with normal appendices, but not compared to the patients with gangrenous appendicitis ( 20 ). Associations have been found between Th17-associated cytokines and complicated appendicitis, indicating that the production of these inflammatory mediators can exaggerate the immune response ( 14 ).…”

Increased IgE Deposition in Appendicular Tissue Specimens Is Compatible with a Type I Hypersensitivity Reaction in Acute Appendicitis

“…Recent evidences suggest the presence of an allergic reaction in AA [30][31][32]. A clinical study showed that Th2 cytokines, IL-4, IL-5, and IL-9, which are known to be involved in allergic responses, are elevated in phlegmonous AA lavage fluids compared with appendectomy specimens obtained after clinical suspicion of AA not histologically confirmed [30].…”

The appendix‐mucosal immunity and tolerance in the gut: consequences for the syndromes of appendicitis and its epidemiology

“…These responses produce histological changes that are described as chronic appendicitis, resolving or focal appendicitis. A wide variety of leucocytes may be seen infiltrating the appendix on histology 42–47 . This is UA, which is here seen to be inflammatory.…”

“…A wide variety of leucocytes may be seen infiltrating the appendix on histology. [42][43][44][45][46][47] This is UA, which is here seen to be inflammatory. Gene expression studies raise the possibility that these patterns may represent viral infection in UA, as opposed to bacterial infection in CA.…”

“…31 Features of these RCTs include a wide array, dose and duration of antibiotics and a low rate of perforation in the antibiotic treatment arms (UA does not become CA [27][28][29] ). This, when combined with the single RCT with a placebo arm Crohn's disease 59 Colon cancer and appendicitis [60][61][62][63][64][65][66][67][68] Chronic ulcerative colitis [54][55][56][57][58]66 Cancer related to Fusobacteria 32,67,68 Fusobacteria polymicrobial [32][33][34][35] SIRS+ Uncomplicated appendicitis 29,31,40,[42][43][44][45]49 Purulent, chronic, focal recurrent Inflammatory 40,[44][45][46][47]54 >1 day Adaptive showing no difference between antibiotic and placebo, 52 suggests that UA is an inflammatory or possibly anti-viral process. 40 Longterm follow-up at 7 years reports a 39% incidence of recurrent appendicitis.…”