title: Interferon-alpha mediates suppression of C-reactive protein: explanation for muted C-reactive protein response in lupus flares?
abstract: OBJECTIVE
  C-reactive protein (CRP) is synthesized by hepatocytes in response to interleukin-6 (IL-6) during inflammation. Despite raised IL-6 levels and extensive systemic inflammation, serum CRP levels remain low during most viral infections and disease flares of systemic lupus erythematosus (SLE). Because both viral infections and SLE are characterized by high levels of interferon-alpha (IFNalpha), the aim of this study was to determine whether this cytokine can inhibit the induction of CRP.
  
  
  METHODS
  The interference of all 12 IFNalpha subtypes with CRP promoter activity induced by IL-6 and IL-1beta was studied in a CRP promoter- and luciferase reporter-transfected human hepatoma cell line, Hep-G2. CRP secretion by primary human hepatocytes was analyzed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  CRP promoter activity was inhibited by all single IFNalpha subtypes, as well as by 2 different mixtures of biologically relevant IFNalpha subtypes. The most prominent effect was seen using a leukocyte-produced mixture of IFNalpha (56% inhibition at 1,000 IU/ml). The inhibitory effect of IFNalpha was confirmed in primary human hepatocytes. CRP promoter inhibition was dose dependent and mediated via the type I IFN receptor. Transferrin production and Hep-G2 proliferation/viability were not affected by IFNalpha.
  
  
  CONCLUSIONS
  The current study demonstrates that IFNalpha is an inhibitor of CRP promoter activity and CRP secretion. This finding concords with previous observations of up-regulated IFNalpha and a muted CRP response during SLE disease flares. Given the fundamental role of both IFNalpha and CRP in the immune response, our results are of importance for understanding the pathogenesis of SLE and may also contribute to understanding the differences in the CRP response between viral and bacterial infections.
authors: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. helena.enocsson@liu.se
authors: Helena
authors: H
authors: Enocsson
authors: Christopher
authors: C
authors: Sjöwall
authors: Thomas
authors: T
authors: Skogh
authors: Maija-Leena
authors: ML
authors: Eloranta
authors: Lars
authors: L
authors: Rönnblom
authors: Jonas
authors: J
authors: Wetterö
mesh_terms: D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism; D002097:C-Reactive Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D014777:Virus Diseases / Q000276:immunology / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D016898:Interferon-alpha; D053583:Interleukin-1beta; D015850:Interleukin-6; D002097:C-Reactive Protein