Interleukin 18 maintains a long‐standing inflammation in coeliac disease patients

Summary Dietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNγ and IL‐15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long‐standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFα, IL‐12(p35), IL‐12(p40), IL‐15, IL‐18 and IL‐23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten‐free diet (GFD), healthy controls, and patients with non‐CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL‐15 and IL‐18 was analysed. Levels of IL‐12 and IL‐23 mRNA are nearly absent, and TNFα levels remain unchanged among different groups. Both the active and inactive forms of IL‐18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL‐15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL‐15 and IL‐18. In active CD, the early response following gluten intake characterized by high IFNγ levels is driven by IL‐18, and probably IL‐15, and this alternates with periods of long‐standing inflammation with moderate IFNγ levels, maintained by IL‐18 alone.