tetano
Editor, Senior Moderator
J Infect Dis. 2018 Sep 10. doi: 10.1093/infdis/jiy527. [Epub ahead of print]
[h=1]Prostaglandin E2-mediated impairment of innate immune response to A(H1N1)pdm09 infection in diet-induced obese mice could be restored by paracetamol.[/h] Zhang AJX[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Zhu H[SUP]4[/SUP], Chen Y[SUP]1[/SUP], Li C[SUP]1[/SUP], Li C[SUP]1[/SUP], Chu H[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Gozali L[SUP]1[/SUP], Lee ACY[SUP]1[/SUP], To KKW[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Hung IFN[SUP]4[/SUP], Yuen KY[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Objective:[/h] To investigate why obesity leads to increased severity of influenza infection.
[h=4]Methods:[/h] We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus.
[h=4]Results:[/h] 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.
[h=4]Conclusions:[/h] 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
[h=1]Prostaglandin E2-mediated impairment of innate immune response to A(H1N1)pdm09 infection in diet-induced obese mice could be restored by paracetamol.[/h] Zhang AJX[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Zhu H[SUP]4[/SUP], Chen Y[SUP]1[/SUP], Li C[SUP]1[/SUP], Li C[SUP]1[/SUP], Chu H[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Gozali L[SUP]1[/SUP], Lee ACY[SUP]1[/SUP], To KKW[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Hung IFN[SUP]4[/SUP], Yuen KY[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Objective:[/h] To investigate why obesity leads to increased severity of influenza infection.
[h=4]Methods:[/h] We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus.
[h=4]Results:[/h] 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.
[h=4]Conclusions:[/h] 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