Enhanced Burn Wound Healing and Conversion Prevention Through Inhibition of High Mobility Group Box 1 in a Scald Burn Rat Model.

Abstract

Severe burns trigger hyperinflammatory and hypermetabolic responses, leading to systemic organ damage. High mobility group box 1 (HMGB1) is an inflammatory peptide released from injured sites. This study investigated wound progression in scald burn rats treated with anti-HMGB1 antibody (Ab). Male Sprague-Dawley rats were divided into sham burn (n&#x2009;=&#x2009;5), burn with vehicle treatment (n&#x2009;=&#x2009;8), and burn with anti-HMGB1 Ab treatment (n&#x2009;=&#x2009;8). After 30% total body surface area burns, rats were treated with chicken IgY (burn/vehicle group) or anti-HMGB1 Ab (burn/treatment group). Skin samples were collected at 3 and 14 days after burn for histological analysis of wound composition and healing. ANOVA and post hoc Tukey tests were used for statistical analysis. Anti-HMGB1 Ab improved healing, increasing epithelial thickness on day 14 compared to sham (58&#xa0;&#x3bc;m&#x2009;&#xb1;&#x2009;22&#xa0;&#x3bc;m vs 21&#xa0;&#x3bc;m&#x2009;&#xb1;&#x2009;3&#xa0;&#x3bc;m; P < .01) and dermal thickness over vehicle (1.7&#xa0;mm&#x2009;&#xb1;&#x2009;0.23&#xa0;mm vs 1.4&#xa0;mm&#x2009;&#xb1;&#x2009;0.25&#xa0;mm; P < .05). Panniculus carnosus muscle loss was lower in the anti-HMGB1 Ab-treated group than vehicle group (-6.4%&#x2009;&#xb1;&#x2009;1.5% vs -70.9%&#x2009;&#xb1;&#x2009;25%; P = .01). High mobility group box 1 expression decreased in epithelium on day 14 (17.15%&#x2009;&#xb1;&#x2009;11.94% vs 60.83%&#x2009;&#xb1;&#x2009;5.28%; P = .02) and dermal inflammation decreased significantly on day 3 (0.45%&#x2009;&#xb1;&#x2009;0.10% vs 4.05%&#x2009;&#xb1;&#x2009;0.49%; P < .0001). Reducing circulating HMGB1 levels decreases burn wound conversion with improved wound healing.