Fig 1.

EP pretreatment prevents endotoxin lethality by attenuating TNF and HMGB1 release in vivo. (a) Mice (n = 20–30 per group) were injected with a single dose of EP as indicated, followed 30 min later by a lethal infusion of endotoxin (5 mg LPS/kg, i.p.). EP conferred significant protection against lethality (P < 0.05), as measured by Fisher's exact test. (b) In a parallel group of EP-treated animals, circulating TNF levels were measured by ELISA of sera prepared at the time indicated after LPS injection (5 mg LPS/kg, i.p.). EP pretreatment (40 mg/kg, i.p.) significantly attenuated the release of serum TNF in response to LPS (* = P < 0.05, by Student's t test). (c) Circulating levels of HMGB1 20 h after LPS infusion (5 mg LPS/kg, i.p.) were measured in a parallel experimental group of endotoxemic animals by Western blot analysis. Pretreatment with EP (40 mg/kg, i.p.) attenuated serum HMGB1 levels at 20 h after LPS (5 mg LPS/kg, i.p.).