Prostaglandin E2-mediated impairment of innate immune response to A(H1N1)pdm09 infection in diet-induced obese mice could be restored by paracetamol.
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UNASSIGNED
To investigate why obesity leads to increased severity of influenza infection.
UNASSIGNED
We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus.
UNASSIGNED
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.
UNASSIGNED
Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment.
