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J Infect Dis. 2018 Sep 10. doi: 10.1093/infdis/jiy527. [Epub ahead of print]
Prostaglandin E2-mediated impairment of innate immune response to A(H1N1)pdm09 infection in diet-induced obese mice could be restored by paracetamol.
Zhang AJX1,2,3, Zhu H4, Chen Y1, Li C1, Li C1, Chu H1,2,3, Gozali L1, Lee ACY1, To KKW1,2,3, **** IFN4, Yuen KY1,2,3.
Author information
Abstract
Objective:
To investigate why obesity leads to increased severity of influenza infection.
Methods:
We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus.
Results:
The lungs of DIO mice were heavily affected by obesity-associated chronic systemic inflammation with a significant increase in inflammatory cytokines/chemokines. Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also significantly elevated in DIO mice. However, the DIO mice mounted a blunted and delayed upregulation of mRNA and protein concentrations of interferon-β and inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md) challenge comparing with those of lean mice. PGE2 concentrations were significantly higher in the lungs of DIO mice comparing to that of lean mice post-challenge. Treatment with paracetamol in challenged DIO mice significantly enhanced the expression of interferon-α/β and cytokine genes at days 1 and 3 post infection comparing with that of untreated DIO mice. Furthermore, paracetamol treatment alone started 3 days before virus challenge and continued till 6 days post-challenge, ameliorated the severity of a lethal H1N1/415742Md infection in DIO mice with improved survival.
Conclusions:
Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment.
PMID: 30202973 DOI: 10.1093/infdis/jiy527
Prostaglandin E2-mediated impairment of innate immune response to A(H1N1)pdm09 infection in diet-induced obese mice could be restored by paracetamol.
Zhang AJX1,2,3, Zhu H4, Chen Y1, Li C1, Li C1, Chu H1,2,3, Gozali L1, Lee ACY1, To KKW1,2,3, **** IFN4, Yuen KY1,2,3.
Author information
Abstract
Objective:
To investigate why obesity leads to increased severity of influenza infection.
Methods:
We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus.
Results:
The lungs of DIO mice were heavily affected by obesity-associated chronic systemic inflammation with a significant increase in inflammatory cytokines/chemokines. Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also significantly elevated in DIO mice. However, the DIO mice mounted a blunted and delayed upregulation of mRNA and protein concentrations of interferon-β and inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md) challenge comparing with those of lean mice. PGE2 concentrations were significantly higher in the lungs of DIO mice comparing to that of lean mice post-challenge. Treatment with paracetamol in challenged DIO mice significantly enhanced the expression of interferon-α/β and cytokine genes at days 1 and 3 post infection comparing with that of untreated DIO mice. Furthermore, paracetamol treatment alone started 3 days before virus challenge and continued till 6 days post-challenge, ameliorated the severity of a lethal H1N1/415742Md infection in DIO mice with improved survival.
Conclusions:
Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment.
PMID: 30202973 DOI: 10.1093/infdis/jiy527