title: Mononuclear cell response to lipopolysaccharide in patients with rheumatoid arthritis: relationship with tristetraprolin expression.
abstract: OBJECTIVE
  To analyze tumor necrosis factor-alpha (TNF-alpha) synthesis by mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  TNF-alpha molecular expression and extracellular release were assessed in the peripheral blood mononuclear cells (PBMC) of 27 RA patients and 16 healthy blood donor controls during 8 hours of LPS stimulation. We also analyzed the mRNA expression of tristetraprolin (TTP), the major TNF-alpha mRNA destabilizing factor. TNF receptor p75 (TNFR 2) plasma concentrations were also tested in all patients.
  
  
  RESULTS
  Controls and patients demonstrated a comparable wide range of TNF-alpha release capability, but patients achieved the peak value of protein release more quickly. Defining the median TNF-alpha release in controls as the cutoff value to distinguish high and low LPS-induced TNF-alpha-releasing phenotypes, patients with early RA (disease duration < 1 yr) belonged mainly to the low TNF-alpha producer subgroup, whereas patients with long-standing RA (> 1 yr) were prevalently high TNF-alpha producers. TTP molecular expression was higher in patients with shorter, than in patients with longer, disease duration. The profile of TNF-alpha release in patients with early RA changed significantly when retested after 6 months of therapy, while patients with long-standing disease maintained the same behavior as at baseline. Finally, a baseline low TNF-alpha-producer phenotype predisposed to a better responsiveness to disease modifying antirheumatic drugs.
  
  
  CONCLUSIONS
  The LPS-induced TNF-alpha-releasing phenotype differs between cells obtained from RA patients with different disease durations and seems to influence the therapeutic outcome.
authors.affiliation: Department of Rheumatology, Universita' Cattolica del Sacro Cuore School of Medicine, Rome, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Fabris
authors.forename: Barbara
authors.initials: B
authors.lastname: Tolusso
authors.forename: Emma
authors.initials: E
authors.lastname: Di Poi
authors.forename: Paola
authors.initials: P
authors.lastname: Tomietto
authors.forename: Stefania
authors.initials: S
authors.lastname: Sacco
authors.forename: Elisa
authors.initials: E
authors.lastname: Gremese
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D018501:Antirheumatic Agents; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D047889:Receptors, Tumor Necrosis Factor, Type II; D051816:Tristetraprolin; D014409:Tumor Necrosis Factor-alpha; C497552:ZFP36 protein, human