RESUMEN
The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects.
Asunto(s)
Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Etanercept/uso terapéutico , Regulación de la Expresión Génica/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Artritis Juvenil/genética , Artritis Juvenil/inmunología , Artritis Juvenil/patología , Estudios de Casos y Controles , Niño , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Interleucina-10/genética , Interleucina-10/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenRESUMEN
The synthesis of a series of novel 1-[(benzofuran-2-yl)phenylmethyl]-triazoles and -tetrazoles is described. The compounds were tested for human placental aromatase inhibition in vitro, using [1beta-3H]-androstenedione as the substrate for the aromatase enzyme, the percentage inhibition and IC50 data is included.