title: The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis.
abstract: 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)-1β, 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.
authors.affiliation: Department of Pediatric Rheumatology, Cohen Children's Medical Center, North-Shore-Long Island Jewish Health System, Lake Success, NY.
authors.forename: H M
authors.initials: HM
authors.lastname: Walters
authors.affiliation: Department of Rheumatology, Hospital for Special Surgery, New York, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Pan
authors.affiliation: Department of Rheumatology, Hospital for Special Surgery, New York, NY, USA.
authors.forename: T J A
authors.initials: TJ
authors.lastname: Lehman
authors.affiliation: Department of Rheumatology, Hospital for Special Surgery, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Adams
authors.affiliation: Department of Rheumatology, Hospital for Special Surgery, New York, NY, USA.|Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, New York, NY, USA.|Department of Medicine, New York, NY, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Kalliolias
authors.affiliation: Clinical and Translational Science Center, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Y S
authors.initials: YS
authors.lastname: Zhu
authors.affiliation: Clinical and Translational Science Center, Weill Cornell Medical College, New York, NY, USA.
authors.forename: F
authors.initials: F
authors.lastname: Santiago
authors.affiliation: Department of Epidemiology and Biostatistics, Hospital for Special Surgery, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Department of Pediatrics, New York, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Sitaras
authors.affiliation: Department of Pediatrics, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cunningham-Rundles
authors.affiliation: Department of Pediatrics, New York, NY, USA.|Department of Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
authors.affiliation: Department of Pediatrics, New York, NY, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Toussi
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002648:Child; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008297:Male; D011446:Prospective Studies; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; C508609:IL10 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000068879:Adalimumab; D000068800:Etanercept
keywords: arthritis; autoimmunity; cytokines