Therapeutic effects of mucosal tolerance on experimental colitis in rats.
OBJECTIVE
To analyze the therapeutic effect of oral tolerance and nasal tolerance singly and in combination with mucosal adjuvant on experimental colitis in rats.


METHODS
Rat models were established using trinitrobenzenesulphonic acid enemas. Ovalbumin was used as inducing antigen and lipopolysaccharide as adjuvant. Colonic scores, splenic mononuclear cell proliferation, and expressions of Toll-like receptors (TLR) and regulatory T cells were determined.


RESULTS
Colonic scores decreased most significantly after ovalbumin and lipopolysaccharide nasal administration (P<0.05). Colonic expression of forkhead box P3 in rats after ovalbumin and lipopolysaccharide oral (P<0.05) and nasal administration (P<0.01) were both significantly higher than untreated rats. TLR2 expression on CD4(+)CD25(+) T cells decreased most significantly after ovalbumin and lipopolysaccharide nasal therapies (P<0.01). TLR4 colonic expression decreased significantly after ovalbumin and lipopolysaccharide oral administration (P<0.05) and lipopolysaccharide oral administration (P<0.05).


CONCLUSIONS
Although experimental colitis prevented oral tolerance, nasal tolerance was successfully induced. The therapeutic effect of nasal tolerance combined with adjuvant produced the best results. TLR downregulation and CD4(+)CD25(+) T cells upregulation were involved in mucosal tolerance.
Shan-Shan
Zhang
Z
Department of Gastroenterology, Peking University People's Hospital, Beijing, China.
Yu-Lan
Liu
L
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007413:Intestinal Mucosa / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D000276:Adjuvants, Immunologic; D000941:Antigens; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014302:Trinitrobenzenesulfonic Acid; D010047:Ovalbumin