title: The burn wound inflammatory response is influenced by midazolam.
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.
authors.affiliation: Department of Research, Shriners Hospital Cincinnati, University of Cincinnati, 3229 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Babcock
authors.forename: Laura
authors.initials: L
authors.lastname: Hernandez
authors.forename: Ekta
authors.initials: E
authors.lastname: Yadav
authors.forename: Sandy
authors.initials: S
authors.lastname: Schwemberger
authors.forename: Amy
authors.initials: A
authors.lastname: Dugan
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D054407:Chemokine CCL4 / Q000097:blood; D054426:Chemokine CXCL2 / Q000097:blood; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008874:Midazolam / Q000008:administration & dosage / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014945:Wound Healing / Q000502:physiology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D008874:Midazolam