Pioglitazone protects from lethal influenza challenge. Prophylactic treatment with pioglitazone significantly decreases host morbidity, presented as mean percentage original body weight ± SEM and representative of 3 independent experiments (n ≥ 5) (interaction effect, P < 0.001; asterisks mark significant simple effects, P < 0.001) (A), increases host survival (Mantel–Cox, P = 0.005) after lethal influenza challenge (103 pfu of PR8) of the pioglitazone-treated group (n = 16) versus PBS-treated controls (n = 23) (B), decreases MCP-1 (CCL2) and MCP-3 accumulation in the BAL wash on days 3 (C) and 6 (D) after infection with 103 pfu of PR8, and decreases tipDC accumulation in the lungs (E). Results are representative of 2 independent experiments (n ≥ 5) and were analyzed with the two-tailed Student's t test (P values are indicated).