Autoimmune diseases adjuvant effect

In induced models, a susceptible animal strain is immunized with a mixture of an adjuvant and an autoantigen isolated from the target organ. Examples are adjuvant arthritis in the Lewis strain rat (Pearson, 1956) and experimental allergic encephalomyelitis, a model of multiple sclerosis (Ben-Nun Cohen, 1982). Induced models are often used to study the pathogenesis of and therapeutic venues for relevant autoimmune diseases. These models have been proposed as means to evaluate the immunomodulatory effects of chemicals on ongoing autoimmune diseases in a second tier of immunotoxicity testing. 

If cholestasis is not present, the additional application of ursodeoxycholic acid (UDCA) is worth considering because of its pharmacological properties and lack of side effects or interactions. Initial results on the treatment of chronic hepatitis with UDCA were reported by F. IcHiDA (1961), T. Nakahara et al. (1975) and K. Miyaji (1976). (s. p. 705) In 1988 our study group also noted obvious and permanent effects of UDCA on the course of disease in terms of clinical and laboratory indices in severe acute viral hepatitis B. (s. p. 437) Such observations were confirmed by A. Jorge in 1993. Owing to the multiple mechanisms of action of UDCA, in particular its immunomodulatory effect, adjuvant therapeutic efficacy can be anticipated in autoimmune hepatitis, as reported by P. Janowitz et al. in 1996. In autoimmune-associated chronic hepatitis C, UDCA proved to be a successful therapeutic agent (K. Nakamura et al., 1999). 

Models of rheumatoid arthritis (RA) were object to l,25(OH)2D3 treatment, providing additional support for the high potential of the hormone for the treatment of Thl-mediated diseases. As an example, in rat adjuvant arthritis l,25(OH)2D3 improved the inhibiting effect of cyclosporine A on arthritis onset as well as on arthritis aggravation [142]. The incidence and severity of type II collagen-induced arthritis was reduced in rats or mice orally treated with 25-(OH)2-D3, the 1,25 (OH)2D3 analog MC 1288 or l,25(OH)2D3 [143-145], l,25(OH)2D3 has further proven to be therapeutically effective in animal models of autoimmune thyroiditis [146], allogeneic transplantation [66, 147,148], rat Heymann nephritis [149] and autoimmune prostatitis [80]. Results from l,25(OH)2D3-related studies in animal models are summarized in Table 10.3. 

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