Cutaneous
burn injury is one of the most devastating
injuries one can obtain, with tissue damage extending beyond the skin
wound to distal organs, including the gastrointestinal tract, liver, and lungs.
Multiple organ failure is a leading cause of death after
burn injury, resulting in excessive systemic and localized
inflammation directly contributing to end organ damage. We postulated that the gut-liver-lung inflammatory axis underscores
multiple organ failure in the context of
burn injury and is hyper-activated when
ethanol intoxication precedes
burn. Mesenchymal stem cells (MSCs) are regenerative and anti-inflammatory, and MSC treatment has been shown to be beneficial in several
immune disorders and injury models. Our objective was to determine whether
intravenous infusion of exogenous bone marrow-derived MSCs could reduce post-
burn and intoxication pulmonary, hepatic, and systemic
inflammation. Vehicle- or
ethanol- (1.6 g/kg) treated mice were subjected to
sham or 15% total body surface area scald
burn. One hour post-injury, mice were given 5 × 105
CFSE-labeled MSCs or
phosphate-buffered saline intravenously (i.v.) and were euthanized 24 h later. We assessed circulating
biomarkers of
inflammation and liver damage, measured
cytokine and
chemokine production, and quantified apoptosis in lung and liver tissue. Compared to intoxicated and burned mice, those treated with MSCs had less cellularity, limited apoptosis, and a slight reduction in the pro-inflammatory
cytokine interleukin-6 (IL-6) and the neutrophil
chemokine, KC (CXCL1) in lung tissue. Mice with MSCs treatment had more dramatic anti-inflammatory effects on systemic and hepatic
inflammation, as serum
IL-6 levels were diminished by 43%, and
il6 and kc expression in liver tissue were markedly reduced, as were
biomarkers of liver damage,
aspartate transaminase (AST) and
alanine transaminase (AST), compared with intoxicated and burned mice. Taken together, our results suggest intravenous MSCs treatment can diminish systemic
inflammation, lessen hepatic damage, and decrease liver and lung apoptosis and
inflammation, indicating MSCs as a novel
therapy for restoring homeostasis of multiple organ systems in intoxicated
burn patients.