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

Abstract

Despite being the most common abdominal surgical emergency, the cause of acute appendicitis (AA) remains unclear, since in recent decades little progress has been made regarding its etiology. Obstruction of the appendicular lumen has been traditionally presented as the initial event of AA; however, this is often the exception rather than the rule, as experimental data suggest that obstruction is not an important causal factor in AA, despite possibly occurring as a consequence of the inflammatory process. Type I hypersensitivity reaction has been extensively studied, involving Th2 lymphocytes, and cytokines such as IL-4, IL-5, IL-9 and IL-13, which have well-defined functions, such as a positive-feedback effect on Th0 for differentiating into Th2 cells, recruitment of eosinophils and the release of eosinophilic proteins and the production of IgE with the activation of mast cells, with the release of proteins from their granules. Cytotoxic activity and tissue damage will be responsible for the clinical manifestation of the allergy. AA histological features are similar to those found in allergic reactions like asthma. The intestine has all the components for an allergic immune response. It has contact with hundreds of antigens daily, most of them harmless, but some can potentially induce an allergic response. In recent years, researchers have been trying to assess if allergy is a component of AA, with their latest advances in the understanding of AA as a Th2 reaction shown by the authors of this article.

Keywords: allergy; appendicitis; appendicular lavage fluid; eosinophils; hypersensitivity type I reaction; mast cells.

Figure 1

Type I hypersensitivity reaction: antigen-presenting cells (APC) present antigens to naive T cells (Th0). Th0 cells will differentiate into Th2 cells, which secrete IL-4, IL-5, IL-9 and IL-13. IL-4 has a positive feedback effect in Th0 cells, because it induces their differentiation into Th2 cells and also influences the differentiation of B cells into IgE-producing cells. The IgE then attaches itself to high-affinity receptors on mastocytes, with antigen binding and crosslinking of IgE antibodies inducing mast-cell granule protein release as a result. IL-5 promotes eosinophil activation, tissue eosinophilia and the release of eosinophil granule proteins, like the Eosinophilic Cationic Protein (ECP) and Peroxidase Eosinophilic (PE). IL-9 is involved in mast-cell proliferation, whereas IL-4 and IL-13 cause smooth-muscle hyperreactivity. IL-13 has similar biological activity to IL-4 (Courtesy of Sofia Guimarães, MD).

Figure 2

IgE immunostaining, acute appendicitis (Courtesy of Hélder Coelho, MD).