Immunological disorders in inflammatory bowel disease and immunotherapeutic implications

Ulcerative colitis and Crohn's disease, also called inflammatory bowel diseases, are characterised by altered mucosal and systemic immune responses. An increase in T helper (h) 1 cytokines, such as interleukin-2 and interferon-gamma, has been found in mucosa from patients affected by Crohn's disease. On the contrary, in patients with ulcerative colitis, mucosal cytokines seem to belong to the Th2 type with an increased release of interleukin-4, and -10. B lymphocytes isolated from lamina propria of patients with ulcerative colitis produce perinuclear anti-neutrophil cytoplasmic antibodies, thus suggesting a status of hyperactivation of these cells in inflammatory bowel diseases, which may lead to autoimmune phenomena. Polymorphonuclear cells and monocytes/macrophages heavily infiltrate the intestinal mucosa and release proinflammatory cytokines, such as interleukin-1, -6, -8 and tumour necrosis factor-alpha. Endotoxins or lipopolysaccharides, major constituents of the gram-negative bacterial cell wall, are present in the circulation of patients with inflammatory bowel diseases and may account for the release of both cytokines and free radicals. Finally, besides immunosuppressive drugs (e.g. cyclosporin A), immunotherapy with neutralising monoclonal antibodies against tumour necrosis factor-alpha has been experimented in Crohn's disease with encouraging results. In addition, novel promising therapeutic approaches in these diseases include the administration of recombinant interleukin-10 or interleukin-11.