Analysis of interleukin-18, interleukin-1 converting enzyme (ICE) and interleukin-18-related cytokines in Crohn's disease lesions.
A local increase of interleukin-18 (IL-18) expression has been recently demonstrated in Crohn's disease (CD), suggesting a role for mature IL-18 (cleaved by ICE protease) in the induction of proinflammatory cytokines and Th1 polarization observed in CD lesions. The aim of this study was to investigate IL-18 modulation and its potential immune consequences in CD lesions. We showed increased IL-18 production in chronic CD lesions and identified epithelial cells and macrophages as IL-18-producing cells. A twofold increase in ICE alpha, beta, and/or gamma mRNA that encodes for the complete mature peptide was required for ICE activity, and a marked increase in IL-18R-positive immune cells was observed in chronic lesions compared to uninvolved areas or normal control samples. Chronic lesions also displayed intense transcription of IL-18-induced cytokines, IFN-gamma, IL-1beta, TNF-alpha, and IL-8. By contrast, when neither IL-18 nor ICE mRNAs were enhanced (early asymptomatic CD lesions), IL-18-induced cytokines were not up-regulated. These results are in accordance with a putative role of mature IL-18 in the pathogenesis of CD.
Laboratoire de Transfert en Imunologie, Universités Paris-V, France. franck.pages@cochin.univ-paris5.fr
F
F
Pagès
V
V
Lazar
A
A
Berger
C
C
Danel
S
S
Lebel-Binay
F
F
Zinzindohoué
P
P
Desreumaux
C
C
Cellier
N
N
Thiounn
D
D
Bellet
P H
PH
Cugnenc
W H
WH
Fridman
D001483:Base Sequence; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D017931:DNA Primers; D020382:Interleukin-18; D012333:RNA, Messenger; D020170:Caspase 1