INTRAVENOUS IMMUNOGLOBULIN (IVIG) TREATMENT OF EXPERIMENTAL COLITIS INDUCED BY DEXTRAN SULFATE SODIUM IN RATS

We investigated the therapeutic effect and immunological action mechan ism of IgG in experimental colitis induced by 3% dextran sulfate sodiu m in rats. Intravenous injection of homologous (rat) IgG (400 mg/kg pe r day) caused a significant suppression of occult blood discharge and ulcerative lesions in the colon, while no suppressive effect was obser ved in the case of heterologous (human) IgG. The positive effect of ra t IgG on the lesions was also clearly shown by the histological examin ations. Generation of proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-alpha) and IL-1 alpha, in the lesions was found to b e inhibited by administration of rat IgG. Little or no suppressive act ion was exerted by human IgG. Careful examination of recruited T cells and macrophages, both of which are thought to play important roles in the development of ulcerative colitis, indicated that rat IgG, but no t its human counterpart, decreased the number of immunocompetent cells in colonic mucosa. Meanwhile, in an in vitro study, both forms of IgG were shown to suppress production of TNF-alpha and IL-1 alpha from la mina propria mononuclear cells isolated from rat colon. These findings suggest that, mainly by suppressing recruitment of immunocompetent ce lls into the lesions, homologous IgG may reduce the occurrence of coli tis.