Cited by 77Influenza Virus Research StudiesInflammatory mediators and NSAID effectsThermal Regulation in Medicine

Pharmacologic Inhibition of COX-1 and COX-2 in Influenza A Viral Infection in Mice

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Carey, Michelle A., Bradbury, J. Alyce, Rebolloso, Yvette D., Graves, Joan P., Zeldin, Darryl C., Germolec, Dori R.·2010·PLoS ONE

Abstract

BACKGROUND: We previously demonstrated that cyclooxygenase (COX)-1 deficiency results in greater morbidity and inflammation, whereas COX-2 deficiency leads to reduced morbidity, inflammation and mortality in influenza infected mice. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effects of COX-1 and COX-2 inhibitors in influenza A viral infection. Mice were given a COX-1 inhibitor (SC-560), a COX-2 inhibitor (celecoxib) or no inhibitor beginning 2 weeks prior to influenza A viral infection (200 PFU) and throughout the course of the experiment. Body weight and temperature were measured daily as indicators of morbidity. Animals were sacrificed on days 1 and 4 post-infection and bronchoalveolar lavage (BAL) fluid was collected or daily mortality was recorded up to 2 weeks post-infection. Treatment with SC-560 significantly increased mortality and was associated with profound hypothermia and greater weight loss compared to celecoxib or control groups. On day 4 of infection, BAL fluid cells were modestly elevated in celecoxib treated mice compared to SC-560 or control groups. Viral titres were similar between treatment groups. Levels of TNF-alpha and G-CSF were significantly attenuated in the SC-560 and celecoxib groups versus control and IL-6 levels were significantly lower in BAL fluid of celecoxib treated mice versus control and versus the SC-560 group. The chemokine KC was significantly lower in SC-560 group versus control. CONCLUSIONS/SIGNIFICANCE: Treatment with a COX-1 inhibitor during influenza A viral infection is detrimental to the host whereas inhibition of COX-2 does not significantly modulate disease severity. COX-1 plays a critical role in controlling the thermoregulatory response to influenza A viral infection in mice.

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Crossref · 10.1371/journal.pone.0011610

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  • The COX-2 inhibitors celecoxib and mesalazine also reduced the mortality rate of mice infected with H5N1 influenza virus when administered in combination with zanamivir.

    “The cyclooxygenase-2 (COX-2) inhibitors celecoxib and mesalazine also reduced the mortality rate of mice infected with H5N1 influenza virus when administered in combination with zanamivir (22).”

    From Into the Eye of the Cytokine Storm (2012) · cites this paper as [22]

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Authors
Carey, M. A., Bradbury, J. A., Rebolloso, Y. D., Graves, J. P., Zeldin, D. C., & Germolec, D. R.
Affiliations
National Institutes of Health (US)
Corresponding author
Zeldin, Darryl C.
Venue
PLoS ONE
Published
2010-07-15
Volume
5
Issue
7
Pages
e11610
ISSN
1932-6203 (ISSN-L)
OpenAlex
W1968602018
Cited by
77
References
42
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 2 · 2018: 8 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 5 · 2012: 6
FWCI
3.72
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
Keywords
influenza A virus, cyclooxygenase-1, cyclooxygenase-2, COX-1 inhibitors, COX-2 inhibitors, SC-560, celecoxib, host-virus interaction, thermoregulation, hypothermia, mortality, inflammation, TNF-α, granulocyte colony-stimulating factor, interleukin-6, KC chemokine, bronchoalveolar lavage, viral infection
MeSH terms
Celecoxib, Animals, Female, Orthomyxoviridae Infections, Influenza A virus, Pyrazoles, Sulfonamides, Cyclooxygenase Inhibitors, Mice, Cyclooxygenase 1, Cyclooxygenase 2

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