Inflammatory bowel disease pathogenesis: therapeutic implications

The pathogenesis of inflammatory bowel disease (IBD) is complex, involving environmental, genetic, microbial, and immune factors. Therefore, treatment should target components that either predispose to or mediate the chronic inflammatory response of IBD. At the moment it is assumed that all components are necessary to have the typical manifestations of IBD but, in reality, it is unclear to what extent each factor contributes to the disease process, and whether some are more important than others. In addition, some factors are not practical targets; for example, environmental factors are poorly defined, too numerous, and require changes that cannot be implemented by the physician or the patient alone. The same is true for genetic factors that are still not amenable to therapeutic manipulations for technical and ethical reasons. This leaves microbial and immune factors as the two categories that can be selected for therapeutic intervention and where all current treatments are focused. The commensal gut flora can be qualitatively or quantitatively modified with antibiotics, probiotics, or diet, and a better characterization of enteric bacteria strains should help greatly in developing more effective therapies. Most current drugs are focused on inhibiting pro-inflammatory molecules produced by immune cells, including biological agents that block specific cytokines such as tumor necrosis factor-alpha. It is anticipated that combination therapies targeting multiple pathogenic components will prove more effective than those blocking single components of IBD pathogenesis.