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  • Title: The prostanoid 15-deoxy-Δ12,14-prostaglandin-j2 reduces lung inflammation and protects mice against lethal influenza infection.
    Author: Cloutier A, Marois I, Cloutier D, Verreault C, Cantin AM, Richter MV.
    Journal: J Infect Dis; 2012 Feb 15; 205(4):621-30. PubMed ID: 22219346.
    Abstract:
    BACKGROUND: Growing evidence indicates that influenza pathogenicity relates to altered immune responses and hypercytokinemia. Therefore, dampening the excessive inflammatory response induced after infection might reduce influenza morbidity and mortality. METHODS: Considering this, we investigated the effect of the anti-inflammatory molecule 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) in a mouse model of lethal influenza infection. RESULTS: Administration of 15d-PGJ(2) on day 1 after infection, but not on day 0, protected 79% of mice against lethal influenza infection. In addition, this treatment considerably reduced the morbidity associated with severe influenza infection. Our results also showed that treatment with 15d-PGJ(2) decreased influenza-induced lung inflammation, as shown by the diminished gene expression of several proinflammatory cytokines and chemokines. Unexpectedly, 15d-PGJ(2) also markedly reduced the viral load in the lungs of infected mice. This could be attributed to maintained type I interferon gene expression levels after treatment. Interestingly, pretreatment of mice with a peroxisome proliferator-activated receptor gamma (PPARγ) antagonist before 15d-PGJ(2) administration completely abrogated its protective effect against influenza infection. CONCLUSIONS: Our results demonstrate for the first time that treatment of mice with 15d-PGJ(2) reduces influenza morbidity and mortality through activation of the PPARγ pathway. PPARγ agonists could thus represent a potential therapeutic avenue for influenza infections.
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