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.
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.
Authors: Fabienne Gally; Beata Kosmider; Michael R Weaver; Kathryn M Pate; Kevan L Hartshorn; Rebecca E Oberley-Deegan Journal: Am J Physiol Lung Cell Mol Physiol Date: 2013-04-26 Impact factor: 5.464
Authors: Su Huang; Bibo Zhu; In Su Cheon; Nick P Goplen; Li Jiang; Ruixuan Zhang; R Stokes Peebles; Matthias Mack; Mark H Kaplan; Andrew H Limper; Jie Sun Journal: J Virol Date: 2019-04-17 Impact factor: 5.103
Authors: Ana Fernandez-Bustamante; Jelena Klawitter; Paul Wilson; Nancy D Elkins; Amanda Agazio; Takahiro Shibata; Koji Uchida; Uwe Christians; John E Repine Journal: Inflammation Date: 2013-10 Impact factor: 4.092