Interleukin 15 mediates epithelial changes in celiac disease.
OBJECTIVE
Villous atrophy and crypt proliferation are key epithelial features of untreated celiac disease. We tried to define whether cytokines such as interleukin (IL)-15, IL-2, IL-4, and IL-7, which share chains of their receptors, could influence the epithelial modifications.


METHODS
Duodenal biopsy specimens (14 treated and 13 untreated celiac patients, 7 controls) were cultured in vitro for 24 hours with or without gliadin (1 mg/mL), IL-15, IL-7, IL-4, or IL-2 (10 ng/mL). Tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were also used in some specimens of untreated celiacs. Epithelial expression of Ki67, FAS, and transferrin receptor (TFR) was detected by immunohistochemistry, and apoptosis by TUNEL technique (percentage of positive enterocytes). IL-15-positive cells were detected by immunohistochemistry in celiac disease and control biopsy specimens; presence of IL-15 was also determined by semiquantitative polymerase chain reaction.


RESULTS
Only IL-15 induced enterocyte expression of Ki67, TFR, and FAS in treated celiac (P<0.01 vs. medium) and enterocyte apoptosis in untreated celiac disease specimens. Anti-IL-15 monoclonal antibodies neutralized gliadin-induced enterocyte TFR and FAS expression in treated celiac and enterocyte apoptosis in untreated celiac disease specimens (P<0.05 vs. gliadin). IL-15-positive cells were increased in untreated celiacs (P<0.001 vs. treated celiacs and controls).


CONCLUSIONS
IL-15 is involved in the modulation of epithelial changes in celiac disease, indicating that this cytokine has an unforeseen role in the pathologic manifestations of celiac disease.
Maiuri
L
L
Department of Pediatrics, University "Federico II," Naples, Italy.
Ciacci
C
C
Auricchio
S
S
Brown
V
V
Quaratino
S
S
Londei
M
M
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001706:Biopsy; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000494:pharmacology*; D053938:DNA Fragmentation; D004386:Duodenum; D005260:Female; D005903:Gliadin / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D019409:Interleukin-15 / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D007583:Jejunum; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D005903:Gliadin