title: Serum IL-33 levels and skin mRNA expression in Behçet's disease.
abstract: OBJECTIVE
  Behçet's disease (BD) is an autoimmune/inflammatory disease characterised by abnormal production of proinflammatory cytokines. Interleukin-33 (IL-33) is a novel cytokine of the IL-1 cytokine family that has been recently implicated in several inflammatory and autoimmune diseases and the association of IL-33 with BD has remained unknown. Here we document for the first time, IL-33 level and its association with BD.
  
  
  METHODS
  Serum IL-33 levels were measured in 46 BD patients (20 patients in active stage) and compared to multiple sclerosis (MS), rheumatoid arthritis (RA) patients and to healthy controls. In parallel, the transcription factor NF-κB that mediates IL-33 transcription was also measured. IL-33 mRNA was also quantified in freshly isolated PBMCs and in skin biopsies by real-time RT-PCR analysis. IL-6 and IL-17 were measured by ELISA.
  
  
  RESULTS
  Serum IL-33 level was significantly higher in active BD patients [159.65 ± 61.7 pg/mL] compared to inactive BD patients [85.57 ± 21.07 pg/mL] (p<0.0001) and healthy controls [70.03±25.95 pg/mL] (p<0.0001). Active BD patients expressed lower IL-33 levels than the control disease group, RA and MS patients [p=0.00021]. The serum IL-33 level in active BD patients was corroborated by IL-33 mRNA expression in fresh PBMC. Patients with active BD with retinal vasculitis showed the highest serum IL-33 level. We further stimulated cultured PBMCs with phorbol myristate acetate (PMA) and ionomycin and macrophages with LPS for 24 h. Following stimulation the levels of IL-33 were increased similarly in PBMC [92.35±24.81 pg/ml] and macrophages [93.10±21.58 pg/ml] in active BD patients compared to healthy controls. NF-κB DNA binding activity was significantly increased in PBMCs of active BD patients particularly in LPS-stimulated macrophages compared to healthy controls. IL-33 mRNA expression in the skin lesions of patients with active BD was significantly increased compared to that in healthy skin biopsies [p=0.00016]. A significant relationship was found between the levels of IL-33 and IL-17 [r=0.533; p=0.0024] and IL-33 and IL-6 [r=0.661, p=0.0015] in 20 active BD patients.
  
  
  CONCLUSIONS
  Elevated IL-33 level in active BD patients was found to correlate with disease activity. Targeting IL-33 should be approached with caution.
authors: Department of Histology and Immunology, Medicine School of Tunis, University Tunis El Manar, Tunis, Tunisia. kamel.hamzaoui@gmail.com.
authors: Kamel
authors: K
authors: Hamzaoui
authors: Wajih
authors: W
authors: Kaabachi
authors: Bessima
authors: B
authors: Fazaa
authors: Leith
authors: L
authors: Zakraoui
authors: Ilhem
authors: I
authors: Mili-Boussen
authors: Faycal
authors: F
authors: Haj-Sassi
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D020381:Interleukin-17 / Q000097:blood; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood* / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C506536:IL33 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D000067596:Interleukin-33; D015850:Interleukin-6; D007378:Interleukins; D016328:NF-kappa B; D012333:RNA, Messenger