LPS rechallenge–induced mortality is significantly higher in male mice than in female mice. (A) Schematic of the experimental design. Age-matched male and female mice were initially challenged IP with 5 mg/kg LPS on day 0, survival was monitored. On day 7, surviving mice were rechallenged with a lethal dose of LPS (35 mg/kg, IP) and monitored for survival. (B) Left: survival curve of male (n = 30) and female (n = 26) mice following the initial 5 mg/kg LPS challenge. Right: survival curve of male (n = 23) and female (n = 19) survivors rechallenged with 35 mg/kg LPS. (C) Independent repeat of the experiment in panel B, including naïve control mice for the LPS rechallenge studies. Left: survival curve of male (n = 15) and female (n = 18) mice following 5 mg/kg LPS challenge. Right: survival curve of male (n = 12) and female (n = 9) survivors rechallenged with 35 mg/kg LPS. As additional control, naïve males (n = 8) and females (n = 8) were challenged with 15 mg/kg LPS to assess baseline susceptibility. Survival curves were analyzed using the log rank (Mantel-Cox) test. P values < .05 were considered to indicate statistical significance.