Biological therapy of inflammatory bowel disease

Abstract

Ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis are defined as inflammatory bowel diseases (IBD). Those diseases involve disorders of numerous immunological mechanisms associated with cellular and humoral immune response. In CD cellular response is considered to be of crucial importance, and dominant cytokines include: tumor necrosis factor alpha (TNF-alpha), interferon gamma (INF-gamma) and interleukins 1beta (IL-1beta), IL-2, IL-6, IL-8, IL-12. In UC, increased expression of Th2 (responsible for humoral response) is observed. It is connected with increased production of interleukins: 4 (IL-4), IL-5, IL-6, IL-10 and TNF-alpha. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is of vital importance in pathogenesis of IBD. Conventional therapy of CD and UC quite commonly fails to bring satisfactory results, therefore an interest in new therapeutic options, that is, biological therapy, gene therapy, hematopoietic stem cell transplantation, and leucapheresis, has aroused recently. Biological therapy is focused on different stages of the inflammatory process. The fundamentals of biological strategy involve neutralization of pro-inflammatory cytokines, use of anti-inflammatory cytokines and inhibition of neutrophil adhesion. Biological therapy is a promising option because it enables to withdraw corticosteroids and immunosuppressive agents or to reduce their dose. Moreover, it shortens the hospital stay, allows to avoid surgical procedures, extends the remission period and improves patients' quality of life. Currently, 2 agents, infliximab and adalimumab, are registered for the biological therapy of CD in Poland.