Abstract 146: 45-Day Protective Effects of Early, Postburn, Single-Dose 17-β Estradiol on Hepatic Proinflammatory Cytokine Production in Burned Rats
BACKGROUND: Immune-mediated organ failure and death following burn injury often result from a response driven by pro-inflammatory cytokines including TNF-α, IL-6, and IL1-β. Several groups, including our own, have pointed to the central role that hepatic tissue may have as a mediator of morbidity and mortality after severe thermal injury. We have previously reported the ability of 17β-estradiol to mitigate the hepatic inflammatory response in the first 24 hours following burns, and hypothesized that a single dose of estrogen post-injury could have long-term effects on hepatic inflammation.
METHODS: Ninety male rats received 3rd degree 40% total body surface area burns, with 3 serving as controls. At 15 min post-insult, animals received a subcutaneous injection of placebo or 0.5 mg/kg 17- β estradiol. Rats were sacrificed and livers harvested at various times over 24 hrs (30m, 1, 2, 4, 6, 8, 12, 18 and 24-hrs post injury). Twelve rats were carried out to 45 days post-injury, and livers were harvested for analysis at that time. We assessed cytokine levels using ELISA.
RESULTS: At all time points, including 45 days post-injury, levels of TNF-α, IL-6, and IL1-β were significantly lower in the group that received 17-β estradiol (p<0.01) when compared to placebo.
CONCLUSIONS: 17-β estradiol down-regulated the hepatic expression of pro-inflammatory cytokines after severe burns to levels that approached levels seen in unburned animals. We demonstrate not only the ability of 17β-estradiol to mitigate hepatic inflammation after severe thermal injury, but also that a single dose given after the insult can produce long-term effects.
- © 2011 by American Heart Association, Inc.