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Critical Care

Open Access

Early administration of parenteral estrogen suppresses the deleterious local and systemic inflammatory response in severe burns

  • JG Wigginton1,
  • PE Pepe1,
  • JW Simpkins2,
  • JW Gatson1,
  • KG Wigginton1,
  • KR Kareem1,
  • JP Minei1 and
  • D Maass1
Critical Care201216(Suppl 1):P465

Published: 20 March 2012


Soon after severe burns, deleterious cytokines are produced and found in the burned skin, including dead tissue in third-degree injuries. This is followed by a systemic surge in these markers and correlated with subsequent multiorgan failure (MOF). In animal models, this response can be somewhat blunted by early debridement, but such early intervention is not usually feasible in most clinical settings. As estrogen is a powerful anti-inflammatory/anti-apoptotic agent, we tested parenteral 17β-estradiol (E2) as a feasible early alternative intervention to dampen the proinflammatory response.


Male rats (n = 168) were assigned randomly to one of three groups: (1) sham (no) burn (n = 8); (2) burn given placebo (n = 80); and (3) burn given E2 (estrogen). Groups 2 and 3 had 40% TBSA third-degree dorsal burns, early fluid resuscitation and 0.5 mg/kg i.p. estrogen (or placebo) 15 minutes post burn. From each group of 80, eight animals were sequentially sacrificed (and burn tissue and blood sampled for IL-6, TNFα, IL-1β) at one of 10 time points as follows: 0.5, 1, 2, 4, 6, 8, 18 and 24 hours and 7 days (7 days only for the eight shams).


In placebos, very high levels of cytokines appeared almost immediately in the echars and circulation, persisting 7 days post burn. In the estrogen group, cytokines, including tissue and circulating IL-6, the greatest predictor of MOF, remained suppressed at all time points, even day 7 (Figure 1).
Figure 1

Burned skin IL-6 levels at day 7.


Early single-dose parenteral estrogen can dramatically suppress both the local and systemic massive proinflammatory responses in severe burns. Based on these data, estrogen may not only be an inexpensive, simple, adjunctive therapy in burn management, it may obviate the need for many subsequent interventions altogether.

Authors’ Affiliations

University of Texas Southwestern Medical Center, Dallas, USA
University of North Texas, Fort Worth, USA


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  2. J Neuroinfl amm. 2009, 6: 30-36. 10.1186/1742-2094-6-30Google Scholar


© Wigginton et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.