title: [CTLA4-Ig interferes and downregulates the proinflammatory activities of rheumatoid synovial macrophages in monoculture].
abstract: OBJECTIVE
  CTLA4-Ig, a biologic agent employed in rheumatoid arthritis (RA) treatment, downregulates the immune response and exerts anti-inflammatory effects acting on different cells including dendritic/T cells interaction and directly on osteoclasts. We investigated the anti-inflammatory effects of CTLA4-Ig in primary monocultures of RA synovial macrophages (SM).
  
  
  METHODS
  SM were obtained, from 8 RA patients (7 F, 1 M; DAS28>5.2) who underwent therapeutic arthroscopic synoviectomy and were cultured in the absence and in the presence of CTLA4-Ig at the concentration of [500 microg/ml], the most reliable dose related to the previous pharmacological clinical and experimental experiences. Inflammatory cytokine (IL-6, TNFalpha, IL-1beta) expression was evaluated by immunocytochemistry (ICC with relative image analysis), western blot (WB), and quantitative real-time polymerase chain reaction (qRT-PCR).
  
  
  RESULTS
  ICC analysis revealed that CTLA4-Ig treatment significantly downregulated cytokine expression (p<0.001 for IL-6, TNFalpha and IL-1beta) when compared to untreated RA SM. WB and qRT-PCR confirmed partially the data.
  
  
  CONCLUSIONS
  CTLA4-Ig was found to exert a direct and significant anti-inflammatory effect on primary monocultures of RA SM, suggesting a therapeutic power in different phases of the disease activity.
authors.affiliation: Laboratorio di Ricerca e Clinica Reumatologica, Dipartimento di Medicina Interna, Università degli Studi di Genova, Viale Benedetto XV, Genoa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Brizzolara
authors.forename: S
authors.initials: S
authors.lastname: Soldano
authors.forename: P
authors.initials: P
authors.lastname: Montagna
authors.forename: A
authors.initials: A
authors.lastname: Sulli
authors.forename: B
authors.initials: B
authors.lastname: Seriolo
authors.forename: B
authors.initials: B
authors.lastname: Villaggio
authors.forename: P F
authors.initials: PF
authors.lastname: Triolo
authors.forename: P
authors.initials: P
authors.lastname: Clerico
authors.forename: L
authors.initials: L
authors.lastname: Felli
authors.forename: L
authors.initials: L
authors.lastname: Molfetta
authors.forename: M
authors.initials: M
authors.lastname: Cutolo
mesh_terms: D000069594:Abatacept; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000473:pathology* / Q000601:surgery; D015153:Blotting, Western; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D013582:Synovial Fluid / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018501:Antirheumatic Agents; C508600:IL6 protein, human; D018796:Immunoconjugates; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000069594:Abatacept