Abstract
Purpose :
We recently demonstrated that prompt inhibition of tumor necrosis factor alpha (TNF-α) improves corneal wound healing and protects the retina and ocular surface following corneal chemical burn. Given that ocular burns also often involve the periocular skin, this study aims to evaluate the efficacy of systemic TNF-α inhibition in treating skin burns.
Methods :
B6.Cg-Tyrc-2J Hrhr/J, hairless mice skin was burned using a 10mm diameter filter paper soaked in 10N HCl. On the left dorsal fat pad, the soaked filter paper was applied for 1 minute (moderate burn) and on the right fat pad for 3 minutes (severe burn). Immediately after the injury, the skin was irrigated for 15 minutes with normal saline and the mice received a single dose of intraperitoneal injection of infliximab, (6.25 mg/kg), or immunoglobulin G (IgG, 6.25 mg/kg) control treatment. Buprenorphine was used for pain control for 3 days, and sulfamethoxazole/trimethoprim antibiotic was added to the drinking water to prevent infection. Animals were followed and photographed for 13 days. The wound closure was calculated as a percentage of closure in relation to the initial size of the wound (10mm in diameter). Tissue histology was assessed using hematoxylin and eosin (H&E) staining.
Results :
All injuries resulted in open wounds within 3 days after the burn. At day 5, the wound area was reduced in anti-TNF-α treated mice by 72.67 ± 7.469% as compared to IgG treated mice with a reduction of 35.07 ± 4.764% (p=0.0353). At day 7, the wound closure was 81.28 ± 4.947% for anti-TNF-α and 68.54 ± 14.5% for IgG, and at day 10, 91.34 ± 3.2% and 89.01 ± 0.0746%, respectively. Both groups achieved complete wound closure in moderate burns by day 13, but only anti-TNF-α treatment achieved complete wound closure in severe burns. All skin burns resulted in damage of the muscle, adipose tissue, and hair follicles, and in severe burns, hyperkeratosis. In preliminary analysis of H&E stainings of IgG treated mice, there were signs of acute inflammatory cells under the epithelium, not seen in anti-TNF-α treated mice.
Conclusions :
Our preliminary data suggests that systemic anti-TNF-α treatment may be efficacious for skin burns. These findings corroborate our published data on ocular burns, and outline the potential importance of prompt TNF-α inhibition as an adjunct to emergency treatment of burns. Further studies are warranted to establish the best dose, mode of delivery, and treatment duration.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.