IL-5 Serum and Appendicular Lavage Fluid Concentrations Correlate with Eosinophilic Infiltration in the Appendicular Wall Supporting a Role for a Hypersensitivity Type I Reaction in Acute Appendicitis

Abstract

Appendicitis is the most common abdominal surgical emergency, but its aetiology is not fully understood. We and others have proposed that allergic responses play significant roles in its pathophysiology. Eosinophils and Interleukin (IL)-5 are involved in a hypersensitivity type I reaction. Eosinophil infiltration is common in the allergic target organ and is dependent on IL-5. In the presence of an allergic component, it is expected that the eosinophil count and IL-5 local and systemic concentrations become elevated. To address this hypothesis, we designed a prospective study that included 65 patients with acute appendicitis (grouped as acute phlegmonous or gangrenous according to the histological definition) and 18 patients with the clinical diagnosis of acute appendicitis, but with normal histological findings (control group) were enrolled. Eosinophil blood counts and appendicular wall eosinophil infiltration were determined. IL-5 levels in blood and appendicular lavage fluid were evaluated. Appendicular lavage fluid was collected by a new methodology developed and standardized by our group. Appendicular wall eosinophil infiltration was higher in acute phlegmonous appendicitis than in gangrenous appendicitis (p = 0.000). IL-5 blood levels were similar in both pathologic and control groups (p > 0.05). In the appendicular lavage fluid, the higher levels of IL-5 were observed in the phlegmonous appendicitis group (p = 0.056). We found a positive correlation between the appendicular wall eosinophilic infiltration and the IL-5 concentrations, in both the blood and the appendicular lavage fluid, supporting the IL-5 reliance in eosinophil local infiltration. We observed the highest presence of eosinophils at phlegmonous appendicitis walls. In conclusion, the present data are compatible with a hypersensitivity type I allergic reaction in the target organ, the appendix, during the phlegmonous phase of appendicitis.

Compilation of Evidence Supporting the Role of a T Helper 2 Reaction in the Pathogenesis of Acute Appendicitis

“…Eosinophil infiltration was higher in APA than in AGA. In ALF, the higher levels of IL-5 were also observed in the APA group [19].…”

“…A positive correlation was found between the appendicular-wall eosinophilic infiltration and the IL-5 concentrations in both blood and ALF [19].…”

“…Several recent studies have reinforced the hypothesis that there is a Th2 immune reaction in AA [19,45,47,[49][50][51][52][53][54][55][56][57][58][59] (Table 1).…”

“…We designed a prospective study in order to evaluate eosinophil and IL-5 serum levels, together with IL-5 ALF levels and appendicular-wall eosinophilic infiltration. The study included 65 patients with AA and 18 patients in the control group, as they were clinically diagnosed with AA, submitted to appendectomy, and had normal appendicular histological findings [19].…”

“…IL-4 has a positive feedback effect on Th2 cells and induces the differentiation of B cells into IgE-producing cells [17,18]. IL-5 interferes with all aspects of eosinophil activity, being called a chemotactic factor for eosinophils [17][18][19]. IL-9 interferes with the activity of eosinophils, mast cells and lymphocytes [18].…”