Fig. 1.

The anti-inflammatory and protective actions of exogenously administered OLDA in endotoxemic mice. A OLDA increases IL-10 and reduces circulating IL-6 and CCL2 levels in mice challenged with the TLR4 agonist LPS: Wild-type mice were challenged with LPS (1 mg/kg, i.v.) and immediately after with OLDA (10 mg/kg, i.v.) or vehicle (i.v.). IL-10, IL-6, and CCL2 were quantified in plasma at 2 h. Global TRPV1 genetic deficiency reversed the anti-inflammatory effects of OLDA (i.v.; 9- to 12-week male and female, n = 13–17/group). B OLDA reduces the severity of endotoxemic shock: Wild-type mice were treated with LPS (3 mg/kg, i.v.) and immediately thereafter with OLDA (10 mg/kg, i.v.) or vehicle (i.v.). B1 Shows reduced Mouse Sepsis scores (MSS) in mice treated with OLDA. The diagram in B2 shows a representation of average score for each item in the mouse sepsis score (from 0 (healthy) to 4 (very sick)) at 24 h (9- to 12-week male, n = 5–10 per group and time point, total n = 52). C OLDA induces an early rise in plasma IL-10: Wild-type mice were treated with LPS (3 mg/kg, i.v.) followed by OLDA (10 mg/kg, i.v.) or carrier (i.v.). Plasma IL-10 levels were significantly increased at 2 h, but not at 12 or 24 h in mice treated with OLDA (9- to 12-week male, n = 5 per group and time point, total n = 35). D OLDA administration reduced activation CD4+ spleen T cells in endotoxemic shock (9- to 12-week male, n = 7/group for LPS and LPS + OLDA groups, and n = 3/group for saline controls). *P < 0.05, **P < 0.01, ***P < 0.001, two-tailed Mann–Whitney U test