Effects of Immunostimulatory DNA Oligonucleotides on Experimental Colitis

Abstract

The etiology of human inflammatory bowel disease (IBD) is not yet known, and its pathogenesis is also poorly understood. At present, an uncontrolled or downregulated cellular immune response to an unknown trigger seems to play an important role. CD4+ T-cells were suggested to have a central role in the pathogenesis of experimental colitis (1) and human IBD, since in the latter, the CD4+ T cell pool is expanded both in the peripheral blood and in the inflamed mucosa (2). The balance between the three subsets of CD4+ T cells, which is well regulated under normal circumstances, is interrupted in several disease states. Human Crohn’s disease (CD) is thought to be characterized by Th-1 response, which produces IL-2, IFN-γ, and tumor necrosis factor (TNF-α). Ulcerative colitis (UC) is dominated by Th-2 response, which produce antiinflammatory cytokines, such as; IL-4, IL-5, and IL-10. Models of experimental colitis also vary according to the dominant phenotype of Th-1 or Th-2 response. Spontaneous colitis in IL-10 knockout (KO) mice is mediated predominantly by Th-1 response (3). Tri or dinitrobenzene sulphonic acid induced colitis is characterized by predominant Th-2 response, and in this respect mimics UC (4). Administration of dextran sodium sulphate (DSS) to immune competent mice induce acute and chronic colitis, with features characteristic of a mixed Th-1/Th-2 response (1).