Immunoregulatory effects of local and systemic use of melatonin in experimental thermal trauma

Abstract

High incidence of thermal trauma (TT), increased risk of infectious and non-infectious short- and long-term complications, and limited effectiveness of the therapeutic approaches are the main pre-requisites for searching and pathogenetic justification of new therapies. E.g., melatonin, an endogenous homeostatic regulator with pleiotropic properties, deserves special attention. The aim of the work was to study the effect of local application (as an original dermal film) and systemic usage of melatonin upon concentrations of circulating TNF and IL-4 in the course of experimental thermal trauma. The rates of wound epithelization were expressed as per cent values. The plasma concentrations of IL-4, TNF were determined with automatic enzyme immunoassay analyzer Personal LAB (Italy). In the series with TT, the rate of wound epithelization increased from the 5th to the 20th day of experiment. When using dermal films with MT in experimental TT on days +5, +10 and +20, an increase in the rate of wound epithelization was registered. Under the conditions of intraperitoneal MT injection in experimental TT, the rate of wound epithelization increased on days +10 and +20. A correlation analysis revealed stronger interrelations observed when applying dermal films with MT in thermal trauma, rather than in series with intraperitoneal usage of MT thus suggesting faster repair processes in the first case, along with diminished area of alterations and decreased amounts of cytokines in serum. In experimental TT, the concentrations of TNF and IL-4 increase in blood serum on days +5, +10 and +20. On days +10 and +20, moderate positive associations were recorded between the rate of wound epithelialization and the concentration of serum cytokines. Upon intraperitoneal use of MT in experimental TT, on days +5, +10 and +20, the rate of epithelization increases, along with decrease of TNF concentration on days +10 and +20. On days +5, +10 and +20, moderate negative associations were recorded between the rate of wound epithelization and the concentration of TNF. Under the conditions of using DP with MT with TT, the rate of wound epithelization increases on days 5, 10 and 20, the concentration of TNF decreases in serum, the concentration of IL-4 decreases on day +10. On days +5, +10 and +20, the negative correlations were recorded between the rate of wound epithelization and serum concentrations of TNF and IL-4. A comparative efficiency analysis of MT-containing dermal films versus intraperitoneal use of MT in experimental thermal trauma revealed a more accelerated epithelization of the wound along with earlier decrease in TNF, a greater number and strength of relationships between the rate of the wound epithelization and concentrations of cytokines in blood serum.