Immunological disorders in inflammatory bowel disease and immunotherapeutic implications

Ulcerative colitis and Crohn's disease, also called inflammatory bowel dise ases, are characterised by altered mucosal and systemic immune responses. A rt increase in T helper (h) 1 cytokines, such as interleukin-2 and interfer on-gamma, has been found in mucosa from patients affected by Crohn's diseas e. On the contrary, in patients with ulcerative colitis, mucosal cytokines seem to belong to the Th-2 type with an increased release of interleukin-4, and -10. B lymphocytes isolated from lamina propria of patients with ulcer ative colitis produce perinuclear anti-neutrophil cytoplasmic antibodies, t hus suggesting a status of hyperactivation of these cells in inflammatory b owel diseases, which may lead to autoimmune phenomena. Polymorphonuclear ce lls 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 constituen ts of the gram-negative bacterial cell wall, are present in the circulation of patients with inflammatory bowel diseases and may account for the relea se of both cytokines and free radicals. Finally, besides immunosuppressive drugs (e.g. cyclosporin A), immunotherapy with neutralising monoclonal anti bodies against tumour necrosis factor-alpha has been experimented in Crohn' s disease with encouraging results. In addi tion, novel promising therapeut ic approaches in these diseases include the administration of recombinant i nterleukin-10 or interleukin-11.