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

Oral tolerance is an immunological phenomenon that results from protein intake and that has systemic effects on inflammation. Previous research has shown that parenteral injection of tolerated proteins reduces inflammatory infiltrate and improves skin wound healing. Herein, we tested whether the injection of tolerated proteins improves the healing of several wounds on different parts of the body, such as on the skin of the back and on the external ear (the auricle). To induce oral tolerance to ovalbumin (OVA), eight-week old C57BL/6 mice drank egg white diluted 1:5 in water for 3 consecutive days. The control mice drank water. Seven days after oral treatment, mice were submitted to excisional injuries on the skin of the back (6 mm) and ears (4 mm). Minutes before the injuries, the mice received an intraperitoneal injection of OVA + Al(OH)3. Seven and 40 days after the injuries, tissue samples were collected and processed for histological analysis of the wounds. The results showed that the injection of OVA in animals that drank OVA reduced the inflammatory infiltrate in all lesions. In addition, 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 on 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 on different parts of the body.