The effects of immunosuppressive agents on cytokines

Controlled clinical trials have shown that several immunosuppressive drugs are efficacious in patients with inflammatory bowel disease. These drugs each have multiple effects on the immune system and the exact mechanism of their beneficial effect in inflammatory bowel disease is unknown. None of these agents directly inhibits the 'inflammatory cytokines' such as IL-1 beta, IL-6, IL-8, or TNF-alpha. However, they can all inhibit generation of leukocyte precursors in the bone marrow, that is, the cells that produce such cytokines. The effects of current agents on T-cell subsets and their associated cytokines remains unclear. Based on insights from novel mouse models of chronic colitis, the goal of 'immunotherapy' going into the next decade should be either to inhibit specifically the effector T cells mediating disease or to enhance the regulatory T cells that inhibit such effector cells or, ideally, to do both. Therapy meeting this goal, which will need to based on a more thorough understanding of the immunopathogenesis of inflammatory bowel disease, should allow a more specific or 'surgical' approach to immunotherapy and simultaneously reduce its risks and adverse effects.