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Research ArticleInflammation, Immunopharmacology, and Asthma

Acetaminophen Attenuates House Dust Mite–Induced Allergic Airway Disease in Mice

Gregory J. Smith, Roger S. Thrall, Michelle M. Cloutier, Jose E. Manautou and John B. Morris
Journal of Pharmacology and Experimental Therapeutics September 2016, 358 (3) 569-579; DOI: https://doi.org/10.1124/jpet.116.233684
Gregory J. Smith
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (G.J.S., J.E.M., J.B.M); Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut (R.S.T.); Connecticut Children’s Medical Center, Hartford, Connecticut (M.M.C.)
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Roger S. Thrall
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (G.J.S., J.E.M., J.B.M); Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut (R.S.T.); Connecticut Children’s Medical Center, Hartford, Connecticut (M.M.C.)
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Michelle M. Cloutier
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (G.J.S., J.E.M., J.B.M); Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut (R.S.T.); Connecticut Children’s Medical Center, Hartford, Connecticut (M.M.C.)
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Jose E. Manautou
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (G.J.S., J.E.M., J.B.M); Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut (R.S.T.); Connecticut Children’s Medical Center, Hartford, Connecticut (M.M.C.)
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John B. Morris
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (G.J.S., J.E.M., J.B.M); Department of Immunology, University of Connecticut Health Center, Farmington, Connecticut (R.S.T.); Connecticut Children’s Medical Center, Hartford, Connecticut (M.M.C.)
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Abstract

Epidemiologic evidence suggests that N-acetyl-para-aminophenol (APAP) may play a role in the pathogenesis of asthma, likely through pro-oxidant mechanisms. However, no studies have investigated the direct effects of APAP on the development of allergic inflammation. To determine the likelihood of a causal relationship between APAP and asthma pathogenesis, we explored the effects of APAP on inflammatory responses in a murine house dust mite (HDM) model of allergic airway disease. We hypothesized that APAP would enhance the development of HDM-induced allergic inflammation. The HDM model consisted of once daily intranasal instillations for up to 2 weeks with APAP or vehicle administration 1 hour prior to HDM during either week 1 or 2. Primary assessment of inflammation included bronchoalveolar lavage (BAL), cytokine expression in lung tissue, and histopathology. Contrary to our hypothesis, the effects of HDM treatment were substantially diminished in APAP-treated groups compared with controls. APAP-treated groups had markedly reduced airway inflammation: including decreased inflammatory cells in the BAL fluid, lower cytokine expression in lung tissue, and less perivascular and peribronchiolar immune cell infiltration. The anti-inflammatory effect of APAP was not abrogated by an inhibitor of cytochrome P450 (P450) metabolism, suggesting that the effect was due to the parent compound or a non-P450 generated metabolite. Taken together, our studies do not support the biologic plausibility of the APAP hypothesis that APAP use may contribute to the causation of asthma. Importantly, we suggest the mechanism by which APAP modulates airway inflammation may provide novel therapeutic targets for asthma.

Footnotes

    • Received March 23, 2016.
    • Accepted July 5, 2016.
  • This work was supported by a President’s Research Award from the University of Connecticut (to J.B.M., J.E.M., R.S.T., and M.M.C.).

  • dx.doi.org/10.1124/jpet.116.233684.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 358 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 358, Issue 3
1 Sep 2016
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Research ArticleInflammation, Immunopharmacology, and Asthma

Acetaminophen Attenuates Allergic Airway Disease

Gregory J. Smith, Roger S. Thrall, Michelle M. Cloutier, Jose E. Manautou and John B. Morris
Journal of Pharmacology and Experimental Therapeutics September 1, 2016, 358 (3) 569-579; DOI: https://doi.org/10.1124/jpet.116.233684

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Research ArticleInflammation, Immunopharmacology, and Asthma

Acetaminophen Attenuates Allergic Airway Disease

Gregory J. Smith, Roger S. Thrall, Michelle M. Cloutier, Jose E. Manautou and John B. Morris
Journal of Pharmacology and Experimental Therapeutics September 1, 2016, 358 (3) 569-579; DOI: https://doi.org/10.1124/jpet.116.233684
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