Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen.

Abstract

Although oral administration of protein antigens may lead to specific immunologic unresponsiveness, this method of immunoregulation has not been applied to models of autoimmune disease. Type II collagen-induced arthritis is an animal model of polyarthritis induced in susceptible mice and rats by immunization with type II collagen, a major component of cartilage. Intragastric administration of soluble type II collagen, prior to immunization with type II collagen in adjuvant, suppresses the incidence of collagen-induced arthritis. Administration of denatured type II collagen has no observable effect on the incidence or severity of the disease. The overall magnitude of the antibody response is not significantly reduced in collagen-fed mice as compared to controls. While the isotype distribution of the anti-collagen antibodies is similar in the two groups, there is a tendency toward reduced IgG2 responses in the collagen-fed mice.Type II collagen-induced arthritis (CIA) is an animal model of polyarthritis induced in susceptible mice and rats by immunization with type II collagen (1, 2). Type II collagen is the major matrix protein of hyaline cartilage. The similarity of the histopathologic changes observed in CIA to those seen in human rheumatoid arthritis has centered interest on the contribution of collagen autoimmunity to the pathogenesis of the human disease. Although humoral and cellular immunity to type II collagen have been shown in CIA, the precise contribution of each to the development of disease has not been established. While T cells have been shown to recognize undenatured and denatured type II collagen (3), the humoral response is restricted to the undenatured, nonrepeating helical antigenic determinants of the collagen molecule (3, 4

Heat Denaturation of Egg‐White Proteins Abrogates the Induction of Oral Tolerance of Specific Th2 Immune Responses in Mice

“…The oral tolerogenicity of heated proteins was demonstrated after prolonged feeding of whey proteins prepared at 90ЊC for 1 h [13], but was questioned by two other reports [14,15]. One reported that collagen-induced arthritis could be suppressed by feeding soluble type II collagen, but not type II collagen heated at 56ЊC for 45 min [14]. The other reported that deaggregated human r-globulin was better than human r-globulin heat aggregated at 63ЊC for 25 min in the induction of oral tolerance [15].…”

A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes

“…Oral administration of antigens is a long-recognized method for inducing systemic immunological tolerance (1,2), and has been proposed as an approach for the treatment or prevention of allergic (3)(4)(5) and autoimmune diseases (6)(7)(8)(9)(10)(11)(12)(13). This approach, however, requires administration of massive amounts of antigens or prolonged feeding of small amounts of antigens, which are then only effective in rather narrow dose ranges.…”

Oral insulin for diabetes prevention in NOD mice: potentiation by enhancing Th2 cytokine expression in the gut through bacterial adjuvant

“…Because of an apparently low risk of adverse effects, a promising approach of Th1/Th2 immune deviation is the mucosal administration of antigen. Peroral administration of target autoantigens has been shown to mitigate or suppress Th1 dependent autoimmune diseases such as experimental autoimmune encephalomyelitis or collagen induced rheumatoid arthritis in rodents [9][10][11]. Dependent on the antigen dose administered there is a deletion or anergy of specific T cells, or an induction of Th2-type antigen reactive T cells.…”