Systemic effects of oral tolerance improve the healing of several and concomitant wounds in different body parts

Abstract

Throughout our lives, we are continually subjected to different situations that can result in several and concomitant wounds to different parts of our body. The healing of these wounds is essential to maintaining health. Inflammation is an important step in wound healing, but in cases of intense or prolonged inflammation, pathological scarring or non-closure of the wound may occur. Assuming that leukocytes participate in wound healing and that it is possible to intervene systemically with inflammation, we investigated a way to promote better repair of multiple wounds that may occur at the same time. Oral tolerance is an immunological phenomenon that result from protein intake and that have systemic effects on inflammation. Previous works have shown that parenteral injection of tolerated proteins reduces the inflammatory infiltrate and improves skin wound healing. Herein we tested whether the injection of tolerated proteins improves the healing of several wounds in different body parts, such as on the skin of the back and in the external ear (the auricle). To induce oral tolerance to ovalbumin (OVA), eight weeks old C57BL/6 mice drank egg white diluted 1:5 in water for 3 consecutive days. Control mice drank water. Seven days after oral treatment, mice were submitted to excisional injuries in the skin of the back (6 mm) and in the ears (4 mm). Minutes before the injuries, the mice received an intraperitoneal injection of OVA + Al(OH)3. Seven and 40 days after injuries, tissue samples were collected and processed for histological analysis of the wounds. The results show that the injection of OVA in animals that drank OVA reduced the inflammatory infiltrate in all lesions. Besides, injection of OVA in animals that drank OVA promoted better organization of the extracellular matrix, with thicker and intertwined collagen fibers in the neodermis, resulting in smaller scars in the skin. Furthermore, the healing area of the ears of OVA-tolerant animals showed chondrocyte aggregates and less obvious fibrous scar tissue compared with control animals. In conclusion, systemic effects of oral tolerance positively influenced the healing of several lesions in different body parts.