tacrolimus and Burns

Discoid lupus erythematosus (DLE) is a most well-known clinical variation of chronic cutaneous lupus erythematosus inside the spectrum of lupus erythematosus (LE). Cutaneous trauma remains a significant and peculiar causative factor for DLE.. We present a case wherein the patient demonstrated unilateral distribution of DLE on a clinically normal appearing occult facial scald of edible oil, representing Koebner phenomenon (KP) i.e. occurrence of a new skin disease at the site of an unrelated and already healed one.. The 53 years old female patient was unique because she experienced DLE on the nasal back.. The injury was totally settled following a month treatment of oral hydroxychloroquine and topical 0.03% tacrolimus ointment. After three months, she encountered an accidental edible oil scald on the right upper cheek. Several small vesicles appeared on a soybean-sized erythema base with a burning sensation.. We review the literature and conclude by discussing important histologic highlights to think about while endeavoring to perceive the fundamental character and pathogenicity of such sores.

Topics: Burns; Erythema; Female; Humans; Hydroxychloroquine; Lupus Erythematosus, Discoid; Middle Aged; Tacrolimus

Delays in treatment of burn injuries can lead to significant morbidity, loss of function, and poor aesthetic appearance. Preventing conversion from partial- to full-thickness burns may help mitigate these sequelae. The pathophysiology of burn wound conversion remains unknown, but an overactive immune response is thought to be implicated. The purpose of this study was to determine whether downregulating the immune response via tacrolimus can decrease burn wound conversion.. Assembly of the microfluidic hydrogels was achieved by embedding microfibers within a hydrogel scaffold composed of a gelatin-alginate blend. Tacrolimus stock solution for intraperitoneal injection was made by re-suspending powdered tacrolimus in DMSO at 10 mg/mL. 24 young (2-4 months) and 24 old (>16 months) mice were given partial thickness burns. The treatment cohort received either tacrolimus ointment with a hydrogel dressing (6 young and 6 old) or an intraperitoneal injection of a tacrolimus solution (6 young and 6 old), while the control cohort only received either only the microcapillary hydrogel dressing or an intraperitoneal injection of saline. Mice were euthanized at day 3 after injury and skin samples were taken. Burn depth was evaluated using Vimentin immunostaining.. In old mice, intraperitoneal injection of tacrolimus was able to significantly reduce burn wound depth compared to intraperitoneal injection of saline (p = 0.011). Similarly in old mice, topical hydrogel with tacrolimus was able to significantly reduce burn wound depth compared to hydrogel alone (p < 0.001). Topical hydrogel with tacrolimus was able to mitigate the detrimental effects of older age on wound conversion, such that burn wounds of older mice treated with tacrolimus hydrogel dressing had similar burn depths as younger mice (p = 0.240).. Utilizing a combination treatment of tacrolimus and microcapillary hydrogel is able to rescue the negative effects of aging and prevent partial- to full-thickness burn wound conversion. Hopefully these findings will encourage deeper investigation into the possible therapeutic advantages of utilizing immunosuppressive agents to decrease morbidity after burn injuries. Future research will need to specifically investigate IL-2 as an inhibitory target in the acute inflammatory cascade of burn injury.

Topics: Aging; Animals; Bandages; Burns; Hydrogels; Mice; Tacrolimus; Wound Healing

Fibulin-5, a multifunctional extracellular matrix protein, is up-regulated in response to mechanical injury and can promote dermal wound healing. This study aimed to explore the role and mechanism of Fibulin-5 in the pathogenesis of post-burn inflammation in thermally-injured mice. Here, we found that Fibulin-5 was up-regulated in the dorsal root ganglion (DRG) of burn-injured mice. After nociceptive behavioral testing, DRG was isolated and cultured to detect the mechanism of Fibulin-5 in thermal injury models by recombinant adenovirus overexpressing Fibulin-5, RT-qPCR, Western Blot, ELISA, AP20187 (an activator of one kind of kinase phosphorylating the α subunit of eukaryotic initiation factor 2, eIF2α), capsaicin (an agonist of transient receptor potential vanilloid (TRPV)-1), and an anti-CGRP neutralizing antibody. Also, the pathological state of skin tissues and the expression of cyclooxygenase 2 and myeloperoxidase were examined by Hematoxylin-Eosin staining and immunohistochemistry, respectively. We found that overexpression of Fibulin-5 attenuated the pain, inhibited the inflammatory response, and improved the pathologic condition induced by burn injury. Fibulin-5 overexpression significantly down-regulated the phosphorylation level of eIF2α and subsequently inhibited the TRPV1 channel and CREB/CGRP signaling. Additionally, anti-CGRP neutralizing antibody dramatically suppressed the inflammatory response induced by burn injury. The results suggest that overexpression of Fibulin-5 attenuates thermal inflammation via suppressing TRPV1/CGRP pathway. This may provide a potential therapy target to alleviate excessive inflammation in burn patients.

Topics: Animals; Burns; Extracellular Matrix Proteins; Ganglia, Spinal; Immunohistochemistry; Inflammation; Mice; Phosphorylation; Receptors, Calcitonin Gene-Related Peptide; Recombinant Proteins; Signal Transduction; Tacrolimus; TRPV Cation Channels; Up-Regulation

Neutrophils diffusely invade lung, liver, kidney, intestine, muscle and burned skin following burn injury. To ameliorate this invasion and minimize its effects, neutrophils can be modulated by giving neutrophil inhibitors and modulators. In this study, FK506 was used to decrease neutrophil infiltration and lipid peroxidation in remote organs (lung, liver, kidney and intestine) in a burned rat model. FK506 is a new major immunosuppressive agent that is known to modulate neutrophils during inflammation. Neutrophil infiltration was assessed indirectly by measuring myeloperoxidase (MPO) activity biochemically in remote organs following 30% full thickness burn injury. Malondialdehyde (MDA), the end product of lipid peroxidation, was measured biochemically in remote organs and plasma to determine if there is a relationship between neutrophil infiltration and lipid peroxidation after burn injury. FK506 was given intramuscularly at the dose of 0.5 and 1.0 mg/kg for three days before burn injury. Thermal trauma to the skin caused a statistically significant increase in MPO activity and MDA content in remote organs. FK506 was effective in reducing lipid peroxidation and neutrophil infiltration especially at 24 h postinjury in lung, liver and kidney. FK506 may have some benefit (prophylactic) in reducing systemic neutrophilic injury and related lipid peroxidation in burns.

Topics: Animals; Biomarkers; Burns; Cell Migration Inhibition; Disease Models, Animal; Follow-Up Studies; Immunosuppressive Agents; Intestinal Mucosa; Kidney; Lipid Peroxidation; Liver; Lung; Male; Malondialdehyde; Neutrophils; Peroxidase; Rats; Rats, Wistar; Tacrolimus

A 30% burn injury was found highly immunosuppressive in mice by means of two in vivo measurements of cell-mediated immunity, and this immunosuppression could be prevented by early excision and grafting. FK506, a new immunosuppressive agent, was given at different doses for 12 days after early excision and grafting following burn and all doses prolonged the acceptance time of allografts from 14 to 20 days. Allograft rejection was not seen when animals were on the drug. Higher doses prolonged the rejection more, even after the cessation of the drug, and they caused some degree of immunodepression. Immunosuppressive treatment with FK506 when used following burn injury affected cell-mediated immunity minimally to moderately when compared to burned control groups.

Topics: Animals; Burns; Dermatitis, Contact; Disease Models, Animal; Female; Graft Survival; Immunity, Cellular; Lymph Nodes; Mice; Mice, Inbred BALB C; Skin Transplantation; Tacrolimus