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Estrogen decreases inflammation and apoptotic signaling in the heart following severe burn injury
Critical Care volume 14, Article number: P584 (2010)
Patients with severe burn injury experience a rapid elevation in multiple circulating proinflammatory cytokines, with the levels correlating with both injury severity and outcome. Accumulations of these cytokines in animal models have been observed in remote organs, however data are lacking regarding early serial heart cytokine levels following burn injury, and the therapeutic effects of estrogen on these levels. Using an animal model, we studied the acute effects of a full-thickness third-degree burn on cardiac levels of IL-1β, IL-6, IL-10, and TNFα. In addition, we analyzed the effect of estrogen on levels of cytochrome C, signifying apoptosis, and levels of NF-κB, signifying inflammation. Here, we hypothesized that acute estrogen treatment decreases inflammation in the heart and blocks the induction of apoptosis.
In this study, 144 male rats received third-degree 40% total body surface area burns. Fifteen minutes following burn injury, the animals received a subcutaneous injection of either placebo or 17β-estradiol (0.5 mg/kg). The hearts were harvested at 0.5, 1, 2, 4, 6, 8, 12, 18, and 24 hours after injury, and the heart cytokine (IL-1β, IL-6, IL-10, TNFα) levels were measured using the ELISA method. In addition, we assessed the cytosolic levels of cytochrome C and NF-κB at the 24-hour time point using western blot analysis.
In the burned rats, 17β-estradiol significantly decreased the cardiac levels of TNFα (~95%), IL-6 (~50%), IL-1β (~25%), and IL-10 (~20%), when compared with the placebo group. In addition, we determined that estradiol treatment restored cytosolic levels of NF-κB (65% increase) at the 24-hour time point. Also, estrogen decreased cytosolic accumulation of cytochrome C (50% reduction) at the 24-hour time point.
Following severe burn injury, estrogens decrease cardiac inflammation and levels of the pro-apoptotic cytochrome C. In addition, estrogen signaling promotes cell survival, as indicated by an increase in NF-κB levels. Importantly, estrogen treatment following burn injury nearly ablated the deleterious burn-induced increase of TNFα in the heart to levels similar to unburned control animals. Elevated cardiac levels of TNFα have previously been linked to a poor outcome.
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Gatson, J., Zang, Q., Maass, D. et al. Estrogen decreases inflammation and apoptotic signaling in the heart following severe burn injury. Crit Care 14, P584 (2010). https://doi.org/10.1186/cc8816
- Estrogen Treatment
- Total Body Surface Area
- Estradiol Treatment
- Remote Organ