Interleukin 18 maintains a long-standing inflammation in coeliac disease patients.
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 IFNgamma 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 TNFalpha, 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 TNFalpha 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 IFNgamma levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNgamma levels, maintained by IL-18 alone.
León
A J
AJ
Department of Paediatrics and Immunology, and Institute of Biology and Molecular Genetics (IBGM), Universidad de Valladolid, Valladolid, Spain.
Garrote
J A
JA
Blanco-Quirós
A
A
Calvo
C
C
Fernández-Salazar
L
L
Del Villar
A
A
Barrera
A
A
Arranz
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D046509:Tissue Culture Techniques
D016207:Cytokines; D018836:Inflammation Mediators; D019409:Interleukin-15; D020382:Interleukin-18; D012333:RNA, Messenger; D005983:Glutens; D007371:Interferon-gamma