title: Cytokine production of stimulated whole blood cultures in rheumatoid arthritis patients receiving short-term infliximab therapy.
abstract: Patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) strategies have an increased susceptibility to infections, especially those caused by intracellular pathogens. In this study we assessed the cytokine production capacity in patients with RA and we further investigated whether anti-TNF therapy modulates the production of pro-inflammatory cytokines involved in the resistance against infections. Whole blood cultures from 10 RA patients and 10 healthy controls were stimulated with heat-killed Candida albicans, Salmonella typhimurium, Staphyloccocus aureus, Aspergillus fumigatus or Mycobacterium tuberculosis and production of interleukin (IL)-1beta, IL-6, IL-10, interferon (IFN)-gamma and TNF-alpha was measured. Before anti-TNF therapy, whole blood cultures from RA patients released significantly less IFN-gamma than healthy controls after stimulation with all tested microorganisms. Short-term anti-TNF therapy did not have an inhibitory effect on the release of the cytokines tested. We conclude that cells of patients with RA have a strongly reduced production capacity of IFN-gamma after bacterial challenge. Although short-term therapy with anti-TNF agents did not further decrease the release of other proinflammatory cytokines, the combination of defective IFN-gamma production in basal conditions and TNF neutralization during anti-TNF therapy is likely to be responsible for the higher susceptibility to infections in patients with RA.
authors.affiliation: Department of Internal Medicine, University Medical Center St. Radboud, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Calin
authors.initials: C
authors.lastname: Popa
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Timothy R D S
authors.initials: TR
authors.lastname: Radstake
authors.forename: Piet L
authors.initials: PL
authors.lastname: van Riel
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Jos W M
authors.initials: JW
authors.lastname: Van der Meer
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D001232:Aspergillus fumigatus / Q000472:pathogenicity; D001773:Blood Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D002176:Candida albicans / Q000472:pathogenicity; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D000069285:Infliximab; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D012016:Reference Values; D012486:Salmonella typhimurium / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab