Cytokine Expression in Healthy and Inflamed Mucosa: Probing the Role of Eosinophils in the Digestive Tract

Abstract

We thus conclude that tissue-dwelling eosinophils show different and distinct cytokine expression patterns under noninflammatory and inflammatory conditions.

Basic Pathogenesis of Eosinophilic Esophagitis

“…IL-5 is a cytokine involved in eosinophil production, survival and activation. IL-5 mRNA is increased in the biopsies of EE patients compared to NL patients ( (28,29) and unpublished data). Peripheral CD4+T cells show an increase in intracellular IL-5 in the blood of EE patients compared to non-atopic non-EE patients (10).…”

Gastrointestinal Eosinophilia

“…[4] Croese and colleagues have reported EE to be present in 1:70,000 adults in an Australian provincial city. [39] Finally, we have noted that EE occurs in 1:2,000 children in the Cincinnati metropolitan area over a 5 year time period [49] (and unpublished findings).…”

“…A recent study has shown that tissue-dwelling eosinophils have distinct cytokine expression patterns under inflammatory or non-inflammatory conditions, with esophageal eosinophils from eosinophilic esophagitis patients expressing relatively high levels of Th2 cytokines. [4] …”

“…[11,[14][15][16][17] Further eosinophil-mediated damage is caused by toxic hydrogen peroxide and halide acids generated by EPO and by superoxide generated by the respiratory burst oxidase enzyme pathway in eosinophils. Eosinophils also generate large amounts of the LTC 4 , which is metabolized to LTD 4 and LTE 4 . These three lipid mediators increase vascular permeability and mucus secretion, and are potent stimulators of smooth muscle contraction.…”

Eosinophilic Esophagitis

“…Microarray analysis of tissues from EoE patients identified a unique EoE gene signature, with eotaxin-3 being the most upregulated gene. Recent studies support a role for IL-13 [71] , while translational studies have shown that esophageal eosinophils express increased IL-4 and IL-13 compared to normal controls [72] . Furthermore, esophageal mRNA expression from children with EoE expresses more IFN-␥ , eotaxin-1 and IL-5 than normal tissue [73] .…”