title: Acetaminophen modulates the transcriptional response to recombinant interferon-beta.
abstract: BACKGROUND
  Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration.
  
  
  RESULTS
  We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-beta treatment. CD-1 mice were administered acetaminophen (APAP), interferon-beta (IFN-beta) or a combination of IFN-beta+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-beta. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IkappaBK/NF-kappaB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points.
  
  
  CONCLUSIONS
  A significant change in the transcriptional response was observed following co-administration of IFN-beta+APAP relative to IFN-beta treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-beta treatment.
authors.affiliation: Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario, Canada. Aaron_Farnsworth@hc-sc.gc.ca
authors.forename: Aaron
authors.initials: A
authors.lastname: Farnsworth
authors.forename: Anathea S
authors.initials: AS
authors.lastname: Flaman
authors.forename: Shiv S
authors.initials: SS
authors.lastname: Prasad
authors.forename: Caroline
authors.initials: C
authors.lastname: Gravel
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
authors.forename: Xuguang
authors.initials: X
authors.lastname: Li
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation; D020869:Gene Expression Profiling; D016899:Interferon-beta / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D011994:Recombinant Proteins; D000082:Acetaminophen; D016899:Interferon-beta