RESUMO
OBJECTIVES: 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.
Assuntos
Síndrome de Behçet/imunologia , Mediadores da Inflamação/sangue , Interleucinas/sangue , Interleucinas/genética , RNA Mensageiro/metabolismo , Pele/imunologia , Adulto , Síndrome de Behçet/sangue , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/genética , Biomarcadores/sangue , Biópsia , Estudos de Casos e Controles , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-17/sangue , Interleucina-33 , Interleucina-6/sangue , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/sangue , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
The objective of this studies is to review clinical and laboratory features of lupus panniculitis. The authors report 3 cases of lupus profundus from a group of 70 lupus erythematosus. In both cases the lupus panniculitis presented as subcutaneous infiltrated and indurated nodules. The diagnosis was confirmed on clinical, histological and therapeutic data. The evolution is slow and is characterised by regression of the inflammatory lesions with treatment by antimalarial drugs. The lupus panniculitis has generally a favorable prognosis.
