Experimental study on the treatment of mouse burn injury combined with smoke inhalation injury using thrombopoietin.

Abstract

Burn injuries complicated by smoke inhalation significantly increase clinical severity and can lead to acute respiratory distress syndrome (ARDS). Inhalation injury is predominantly caused by exposure to toxic combustion gases, with thermal damage from steam being relatively uncommon. Thrombocytopenia is frequently observed in severe burns and is associated with poor outcomes, whereas platelet transfusion can carry clinically important risks. Recombinant human thrombopoietin (rhTPO), a hematopoietic growth factor used clinically for thrombocytopenia, may represent an alternative strategy for improving platelet-related recovery after burn-associated inhalation injury. Female C57BL/6 mice were subjected to a 30% total body surface area (TBSA) full-thickness burn combined with smoke inhalation injury. Mice were randomized into three groups: injury-only control, rhTPO subcutaneous injection group (SIG), and rhTPO nebulized inhalation group (NIG). Treatments commenced 0.5 h post-injury and continued for 3 days. Outcomes included 120-hour survival, arterial blood gas parameters, platelet count, thromboelastography, lung histopathology scores, plethysmography-based pulmonary function, and lung cytokine profiles. Both rhTPO administration routes improved 120-hour survival, increased platelet counts, and improved selected thromboelastography parameters. H&E-based histological assessment showed lower lung injury scores at later time points, and plethysmography-based respiratory parameters improved by 120 h. IL-1β and TNF-α levels were lower in rhTPO-treated groups, whereas IL-6 did not show a consistent decrease and should be interpreted cautiously. rhTPO administration, via either systemic or inhaled route, improved survival and several physiological and histological outcomes in this murine model of burn with smoke inhalation injury. Because this study did not include a healthy/sham control group or direct assays of platelet activation, pulmonary microthrombi, or rhTPO pharmacokinetics, the findings should be interpreted as evidence of therapeutic association rather than proof of a defined anti-inflammatory mechanism beyond the measured platelet-related changes.