Intravenous immunoglobulin (IVIG) treatment of experimental colitis induced by dextran sulfate sodium in rats

Abstract

SUMMARYWe investigated the therapeutic effect and immunological action mechanism of IgG in experimental colitis induced by 3% dextran sulfate sodium in rats. Intravenous injection of homologous (rat) IgG (400 mg/kg per day) caused a significant suppression of occult blood discharge and ulcerative lesions in the colon, while no suppressive effect was observed in the case of heterologous (human) IgG. The positive effect of rat IgG on the lesions was also clearly shown by the histological examinations. Generation of proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-a) and IL-1a, in the lesions was found to be inhibited by administration of rat IgG. Little or no suppressive action 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 not 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-a and IL-1a from lamina propria mononuclear cells isolated from rat colon. These findings suggest that, mainly by suppressing recruitment of immunocompetent cells into the lesions, homologous IgG may reduce the occurrence of colitis.

Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis

“…Histologically, the rectum of the control group exhibited marked inflammatory cell infiltration and erosion. As in a previous study using rats with DSSinduced colitis [18] , the present study revealed marked increases in IL-1β and TNF-α, known to produce primarily by activated macrophages in the control group. In the DSS+PDTC-treated group Ⅱ (mice intraperitoneally …”

An FcRn-Dependent Role for Anti-flagellin Immunoglobulin G in Pathogenesis of Colitis in Mice

“…Since FcRn plays a major role in establishing the steady-state half-life of monomeric IgG by diverting these away from lysosomes and into a recycling pathway that allows IgG antibodies to avoid degradation within both parenchymal cells such as the endothelium and hematopoietic cells themselves23, 24, factors that disrupt this relationship between IgG and FcRn would be expected to diminish IgG antibodies and their ability to drive APC activation and antigen presentation. Therapy with intravenous immunoglobulins (IVIG) blocks circulating IgG interactions with FcRn as one of its mechanisms of action31 and has shown some limited efficacy in both DSS colitis in rodents32 and uncontrolled human clinical studies in patients with IBD 33. Our studies further indicate that the beneficial effects of IVIG in DSS colitis are likely to involve blockade of anti-bacterial IgG interactions with FcRn in APC as shown here.…”

Therapeutic effect of intracolonically administered nuclear factorκB (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis

“…DSS‐induced colitis is produced in hamsters [23], mice [24], and rats [25,26] and is characterized by ulceration, epithelial damage, mucosal or transmural inflammatory infiltrates, and lymphoid hyperplasia [24]. DSS‐induced colitis is thought to be caused by (i) direct cytotoxicity, (ii) interference with the normal interaction between intestinal lymphocytes, epithelial cells, and extracellular matrix, (iii) aberrant modulation of the expression of integrin β 7 receptors, other cell receptors or their functions [27], and (iv) changes in the intestinal microflora population [24].…”