title: Systemic effects of oral tolerance reduce the cutaneous scarring.
abstract: BACKGROUND
  Immunological tolerance refer to the inhibition of specific immune responsiveness and the ingestion of proteins previous to immunization is a reliable method to induce (oral) tolerance. Parenteral exposure to tolerated antigens, in adjuvant, trigger indirect and systemic effects that inhibits concomitant immune responses to other unrelated antigens and also decrease unrelated inflammatory responses. Interesting, intraperitoneal (i.p.) exposure to orally-tolerated proteins soon before an incisional linear skin wound improves the healing by primary intention in mice. An important clinical and surgical objective is to identify strategies to improve wound healing and reduce scarring.
  
  
  OBJECTIVE
  To evaluate whether i.p. injection of an orally-tolerated protein improves wound healing by secondary intention and reduce scarring of full-thickness excisional skin injury.
  
  
  METHODS
  C57Bl/6 mice were turned tolerant to ovalbumin (OVA) by drinking a solution containing OVA; seven days later, they received an i.p. injection of OVA plus Al(OH)3 adjuvant immediately before two full-thickness excisional skin wounds, under anesthesia. The wound healing process was evaluated macro and microscopically after H&E, toluidine blue and Gomori's Trichrome staining. The presence of granulocytes, macrophages, miofibroblasts, fibronectin, collagen I and collagen III was investigated by immunofluorescence and the levels of cytokines by flow cytometry or ELISA. Mice not tolerant to OVA were included as controls.
  
  
  RESULTS
  The i.p. injection of OVA+Al(OH)3 in mice orally tolerant to OVA reduced the subsequent inflammatory response in the wound bed and the cutaneous scarring. There was a change in the pattern of collagen deposition making it more similar to the pattern observed in intact skin. In tolerant mice, mast cells and granulocytes (Ly-6C/G+), were reduced, while lymphocytes (CD3+) were increased in the wound bed. Time course analysis of Th1/Th2/Th17 cytokines and growth factors showed slightly differences between tolerant and control groups.
  
  
  CONCLUSIONS
  Parenteral injection of an orally-tolerated protein has systemic consequences that impair the inflammatory response triggered by skin injury and reduce the cutaneous scarring.
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, MG CEP: 31270-901, Brazil.
authors.forename: Raquel Alves
authors.initials: RA
authors.lastname: Costa
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, MG CEP: 31270-901, Brazil.
authors.forename: Liana Biajoli Otoni
authors.initials: LB
authors.lastname: Matos
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, MG CEP: 31270-901, Brazil.
authors.forename: Thiago Anselmo
authors.initials: TA
authors.lastname: Cantaruti
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, MG CEP: 31270-901, Brazil.
authors.forename: Kênia Soares
authors.initials: KS
authors.lastname: de Souza
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, MG CEP: 31270-901, Brazil.
authors.forename: Nelson Monteiro
authors.initials: NM
authors.lastname: Vaz
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, MG CEP: 31270-901, Brazil. Electronic address: crochac@icb.ufmg.br.
authors.forename: Cláudia Rocha
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D015415:Biomarkers; D002921:Cicatrix / Q000276:immunology* / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007108:Immune Tolerance; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000293:injuries / Q000473:pathology*; D014945:Wound Healing / Q000276:immunology*
chemical_list: D000941:Antigens; D015415:Biomarkers; D016207:Cytokines; D010047:Ovalbumin; D003094:Collagen
keywords: Inflammation; Oral tolerance; Scarring; Skin; Wound healing