Inflammatory responses contribute to the morbidity and mortality of severe @entity683 . Current antiviral therapy offers limited success in treating severe @entity281 with both H1N1 and H5N1 viruses. We evaluated the effect of a neuraminidase inhibitor in combination with immunomodulatory drugs in vitro and in a @entity19 model of @entity683 A @entity281 by determining survival rate, @entity55 markers and histopathology. @entity3756 and @entity7428 significantly improved survival in @entity19 infected with a lethal dose of @entity778 . Prophylactic treatment resulted in survival rates of 40% ( @entity7428 ), 30% ( @entity684 ), 0% ( @entity3756 ), 100% ( @entity7428 / @entity684 ) and 70% ( @entity3756 / @entity684 ). Treatment in a therapeutic setting (24  h post-infection) resulted in 80% ( @entity7428 / @entity684 ) and 40% ( @entity3756 / @entity684 ) survival. @entity3756 and @entity7428 had no effect on virus replication in vitro and in vivo, but significantly @entity55 . A significant reduction in cellular infiltration (10-fold) along with inflammatory cytokines @entity1750 (10-fold), @entity777 (5-fold) and regulated on activation normal T cell expressed and secreted (5-fold) was observed in the animals treated with the combination compared to @entity684 alone. Lung histopathology of @entity19 treated with combinations revealed significantly reduced consolidation, infiltration and @entity3794 compared to @entity684 alone. @entity7428 and @entity3756 reduced H1N1 virus-induced @entity55 and mortality. These data support further development of immunomodulatory agents for severe @entity683 .

Reduction of @entity683 virus-induced XXXX and mortality in animals treated with a phosophodisestrase-4 inhibitor and a selective serotonin reuptake inhibitor.

@entity778 :: ('MESH:D015658', 'Disease') :: ['influenza A H1N1 virus'] @entity684 :: ('MESH:D053139', 'Chemical') :: ['oseltamivir'] @entity7428 :: ('MESH:D020889', 'Chemical') :: ['Rolipram', 'rolipram'] @entity55 :: ('MESH:D011014', 'Disease') :: ['reduced lung inflammation', 'lung inflammation'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity1750 :: ('20296(Tax:10090)', 'Gene') :: ['monocyte chemotactic protein-1'] @entity3794 :: ('MESH:D011658', 'Disease') :: ['alveolitis'] @entity3756 :: ('MESH:D020280', 'Chemical') :: ['Sertraline', 'sertraline'] @entity683 :: ('MESH:D007251', 'Disease') :: ['influenza'] @entity281 :: ('MESH:D007239', 'Disease') :: ['influenza infection', 'H1N1 infection'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['interleukin-6']
@entity55 :: (MESH:D011014,Disease) :: ['lung inflammation']
