Effectiveness of various regimens of systemic anti-inflammatory therapy with glucocorticoids in the development of acute LPS-induced lung damage in the experiment

BACKGROUND: When studying new and effective methods of treating acute respiratory distress syndrome, an immunogenic model of lung injury occupies a special place. To date, the search for the optimal strategy and regimen for the use of glucocorticoids in the development of acute respiratory distress syndromе is relevant.

AIM: The article evaluates the effectiveness of various schemes of systemic anti-inflammatory therapy with glucocorticoids in an experimental model of acute LPS-induced lung injury.

MATERIALS AND METHODS: The study was conducted on 100 outbred male rats. Acute lung injury was modeled using an experimental model of direct acute lung injury by a single intratracheal injection of lipopolysaccharide (LPS) from the cell wall of the bacterium Salmonella enterica (Sigma-Aldrich) at a dose of LD50 (20 mg/kg). All animals were divided into groups (20 each): 1 — intact rats; 2 — control group (LPS + saline); 3 — LPS + dexamethasone 0.52 mg/kg (small doses); 4 — LPS + dexamethasone 1.71 mg/kg (average doses); 5 — LPS + dexamethasone 8 mg/kg (high doses). The drugs were administered intraperitoneally once a day for 3 days. Dexamethasone doses were calculated using the interspecies dose transfer method using a factor that takes into account differences in body surface area.

RESULTS: It has been established that an experimental model based on the endotracheal administration of S. enterica leads to the development of mortality from pulmonary causes. According to a preclinical study, the systemic use of low doses of dexamethasone (0.52 mg/kg) was found to be better than higher doses (1.71 mg/kg, 8 mg/kg) in the treatment of acute LPS-induced lung injury.