title: Interleukin-1β measurement in stimulated whole blood cultures is useful to predict response to anti-TNF therapies in rheumatoid arthritis.
abstract: OBJECTIVE
  In RA, response to TNF blockers may be associated with a profile of cytokine production unique to each patient. This study sought to predict the response to biologic agents by examining pro-inflammatory cytokine synthesis in stimulated whole blood cultures (WBCs).
  
  
  METHODS
  We measured the concentration of TNF-α, IL-1β and IL-6 in supernatants of lipopolysaccharide (LPS)-stimulated WBCs obtained from RA patients (n = 41) before anti-TNF therapy (infliximab, 13; etanercept, 26; and adalimumab, 2) and from healthy controls (n = 12). At 24 weeks after biologics, whole bloods were again drawn from 14 of 41 patients. Response was defined by the European League Against Rheumatism response criteria after 24 weeks of therapy.
  
  
  RESULTS
  Among 41 patients, 32 were responders (good 14/moderate 18), while 9 were non-responders. All cytokines measured were significantly lower in RA patients than in controls. In RA, IL-1β production was lower in non-responders than in responders [median (interquartile range): 3.5 (1.5-9.4) vs 10.0 (5.1-93.1) pg/ml, P = 0.048]. The area under the curve from a receiver operating characteristic curve analysis for the prediction of response using IL-1β was 0.717 (95% CI 0.520, 0.914). The sensitivity and specificity of IL-1β (cut-off value 4.84 pg/ml) was 78.1 and 77.8%, respectively. All cytokines were significantly higher 6 months later compared with their respective baseline.
  
  
  CONCLUSIONS
  IL-1β measurement in LPS-stimulated WBC is useful to predict responsiveness to anti-TNF agents. Cytokine production capacities in LPS-stimulated WBCs are up-regulated by biologics.
authors.affiliation: Division of Rheumatology, Jichi Medical University, Saitama Medical Center, 1-847 Amanuma-cho, Omiya-ku, Saitama, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Kayakabe
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sakurai
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ikeuchi
authors.forename: Anastasie Tshilela
authors.initials: AT
authors.lastname: Kadiombo
authors.forename: Toru
authors.initials: T
authors.lastname: Sakairi
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Akito
authors.initials: A
authors.lastname: Maeshima
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D000069285:Infliximab; D053583:Interleukin-1beta / Q000032:analysis / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011237:Predictive Value of Tests; D012372:ROC Curve; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept