title: Antimalarial drugs inhibit IFNα-enhanced TNFα and STAT4 expression in monocytes: implication for systemic lupus erythematosus.
abstract: OBJECTIVE
  To analyse the influence of IFNα on TNFα production by human peripheral blood mononuclear cells (PBMCs), as well as the possible interference of this cytokine on the effect of antimalarial drugs, TNFα regulators widely used in the treatment of systemic lupus erythematosus (SLE).
  
  
  METHODS
  PBMCs, monocytes or T cells were treated with IFNα alone or simultaneously to cellular stimuli as well as in the presence or absence of chloroquine. Supernatants from such cultures were collected to quantify TNFα by ELISA. TNFα and STAT4 expression in cultured cells were analysed by intracellular flow cytometry. In addition, STAT4 gene expression and serum levels of TNFα and IFNα were quantified in 53 SLE patients and 45 controls.
  
  
  RESULTS
  IFNα alone did not modify significantly TNFα production, but an increase was observed in stimulated PBMC. Further analyses showed that monocytes were the cellular population responsible for this effect. In addition, IFNα treatment increased STAT4 in stimulated monocytes, suggesting that TNFα upregulation could be mediated by STAT4. On the other hand, the analysis of the antimalarial effect showed that chloroquine was able to inhibit in vitro the expression of TNFα and STAT4 enhanced by IFNα. In antimalarial-treated SLE patients, however, only those with high IFNα serum levels presented lower expression of STAT4.
  
  
  CONCLUSIONS
  IFNα treatment enhances the induction of TNFα and STAT4 in stimulated monocytes, an effect inhibited in vitro by chloroquine treatment. However, the consequence of antimalarial treatment on SLE patients could be different depending on their IFNα serum levels.
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain. Electronic address: lopezpatricia@uniovi.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: López
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain. Electronic address: rodriguezcjavier@uniovi.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez-Carrio
authors.affiliation: Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain. Electronic address: anasua@uniovi.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050797:STAT4 Transcription Factor / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000962:Antimalarials; D016898:Interferon-alpha; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D014409:Tumor Necrosis Factor-alpha; D002738:Chloroquine
keywords: Antimalarial therapy; IFNα; STAT4; Systemic lupus erythematosus; TNFα