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The Burn Wound Inflammatory Response Is Influenced by Midazolam

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Abstract

Burn patients requiring hospitalization are often treated for anxiety with benzodiazepines (BDZs). Benzodiazepines are reported to influence immune system function. Immune system alterations are a major cause of burn-induced mortality. We wanted to determine whether the BDZ, midazolam given daily at an anxiolytic dose, had any influence on the burn injury-induced inflammatory response in the blood and wound. Mice received a 15% total body surface area flame burn and received either midazolam 1 mg/kg i.p. or saline 0.1 ml daily. Blood and skin wounds were harvested 24 h after injection on post-burn day 2, 3, 7, or 8. Mice treated with midazolam had significantly lower serum IL-1β (p = 0.002), TNF-α (p = 0.002), IL-6 (p = 0.016), IL-10 (p = 0.009), and TGF-β (p = 0.004) than saline-treated mice, with little impact on serum chemokine levels. In the wound, TNF-α and IL-10 were the only cytokines significantly influenced by the drug, being lower (p = 0.018) and higher (p = 0.006), respectively. The chemokines in the wound influenced significantly by midazolam were MIP-1α, MIP-1β, and MIP-2 while MCP-1 and KC were not. There were more inflammatory cells at the burn wound margin in midazolam-treated mice on post-burn day 3. Although serum nitrate/nitrite was significantly increased by midazolam (p = 0.03), both eNOS and iNOS mRNA expression in the wound were similar to the saline group. We found that midazolam given daily after burn injury significantly influenced the inflammatory response. The clinical implications of these findings on wound healing and shock following burn injury, especially larger burns, deserve further investigation.

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ACKNOWLEDGMENTS

We appreciate Erin Pangallo and Mike Murawsky for their technical assistance and help with the animal care. We thank Dr. Steve Boyce for his help with the planimetry. We also thank Greg Noel and Nelson Horseman for their helpful suggestions. This work was funded by the Shriners of North America.

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Authors and Affiliations

  1. Department of Research, Shriners Hospital Cincinnati, University of Cincinnati, 3229 Burnet Avenue, Cincinnati, OH, 45229, USA

    George F. Babcock, Sandy Schwemberger & Amy Dugan

  2. Molecular Cellular Physiology, University of Cincinnati, Cincinnati, OH, USA

    Laura Hernandez, Ekta Yadav & Amy Dugan

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  1. George F. Babcock
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Correspondence to Amy Dugan.

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Babcock, G.F., Hernandez, L., Yadav, E. et al. The Burn Wound Inflammatory Response Is Influenced by Midazolam. Inflammation 35, 259–270 (2012). https://doi.org/10.1007/s10753-011-9313-9

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  • DOI: https://doi.org/10.1007/s10753-011-9313-9

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