The effect of local and systemic administration of L-thyroxine on rate of regeneration and cytokine secretion in experimental burn wound model

BACKGROUND: Thermal skin injuries are among the most common traumatic lesions in humans; however, overall treatment outcomes for deep burns remain unsatisfactory. Thyroid hormones are key regulators of cellular processes, including cell proliferation and angiogenesis, which makes them potential stimulators of regeneration in skin injuries. AIM: The work aimed to investigate systemic and topical effects of L-thyroxine on the wound healing process in an experimental model of deep burn wounds. METHODS: The effect of pharmacologically altered thyroid status and 10 µg/mL thyroxine-containing hydrogel on an experimental third-degree (IIIB) skin burn was studied in 74 white non-linear male rats weighing 220–257 g. A third-degree (IIIB) burn was induced in the proximal dorsal region. Seventy-two hours after burn induction, the eschar was completely excised along the border with intact skin, and a splinting ring was applied; subsequently, in groups Ib and IIIa, the investigational drugs were applied topically. On day 10 after burn induction, levels of interferon gamma (IFN-γ), alpha-defensin 1 (DEFa1), transforming growth factor β1 (TGF-β1), and fibroblast growth factor 2 (FGF2) were measured in wound exudate using enzyme-linked immunosorbent assay. Changes in burn wound area were assessed over time using the Universal Desktop Ruler software. RESULTS: Median time to 50% epithelialization in systemic and local hyperthyroidism groups was 20 (19; 21.5) and 21 (18; 22) days, respectively, significantly shorter than in the intact control group. Median time to 75% epithelialization in all experimental groups differed significantly from both control groups: in systemic and local hyperthyroidism groups, it was 29.5 (28; 32), 30.2 ± 0.9, and 33.3 ± 0.45 days, respectively; in propylthiouracil-induced hypothyroidism group, median time to 75% epithelialization was not reached. In systemic hyperthyroidism group, IFN-γ, DEFa1, TGFβ1, and FGF2 levels in wound exudate, and in local hyperthyroidism group, FGF2 and IFN-γ levels, were significantly higher than in both control groups. In contrast, in propylthiouracil-induced hypothyroidism group, FGF2 and IFN-γ levels were significantly lower compared with control groups. CONCLUSION: Systemic hyperthyroidism and application of thyroxine-containing gel to wound surface accelerate natural wound healing. Thyroid hormones exhibit dose-dependent effects on FGF2 and IFN-γ secretion.