Acetaminophen modulates the transcriptional response to recombinant interferon-beta.
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.
Farnsworth
Aaron
A
Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario, Canada. Aaron_Farnsworth@hc-sc.gc.ca
Flaman
Anathea S
AS
Prasad
Shiv S
SS
Gravel
Caroline
C
Williams
Andrew
A
Yauk
Carole L
CL
Li
Xuguang
X
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
D011994:Recombinant Proteins; D000082:Acetaminophen; D016899:Interferon-beta