Burn injury is associated with muscle wasting, though the involved signaling mechanisms are not well understood. In this study, we aimed to examine the role of high mobility group box 1 (
HMGB1) in signaling hyper-
inflammation and consequent skeletal muscle impairment after
burn. Sprague Dawley rats were randomly assigned into three groups: (1)
sham burn, (2)
burn, (3)
burn/treatment. Animals in group 2 and group 3 received scald
burn on 30% of total body surface area (TBSA) and immediately treated with chicken
IgY and anti-HMGB1 antibody, respectively. Muscle tissues and other samples were collected at 3-days after
burn. Body mass and wet/dry weights of the hind limb muscles (total and individually) were substantially decreased in
burn rats. Acute
burn provoked the mitochondrial stress and cell death and enhanced the
protein ubiquitination and LC3A/B levels that are involved in protein degradation in muscle tissues. Further, an increase in muscle inflammatory infiltrate associated with increased differentiation, maturation and proinflammatory activation of bone marrow myeloid cells and αβ CD4+ T and γδ T lymphocytes was noted in in circulation and spleen of
burn rats. Treatment with one dose of
HMGB1 neutralizing antibody reduced the
burn wound size and preserved the wet/dry weights of the hind limb muscles associated with a control in the markers of cell death and autophagy pathways in
burn rats. Further, anti-HMGB1 antibody inhibited the myeloid and T cells inflammatory activation and subsequent dysregulated inflammatory infiltrate in the muscle tissues of
burn rats. We conclude that neutralization of HMGB1-dependent proteolytic and inflammatory responses has potential beneficial effects in preventing the muscle loss after severe
burn injury.