Anti-inflammatory activity of ansamycins

Inflammation represents a complex biologic and biochemical process involving cells of the immune system and a plethora of biologic mediators in response to mechanical, chemical or infectious injuries. When mobilization of effector cells and molecules becomes excessive, the beneficial aspect of this response--to limit damage and promote healing, can be overriden, resulting in host-cell and tissue dysfunction. Based on the hypothesis that chronic infections underly some inflammatory diseases, antibacterial therapy has long been assessed in various inflammatory settings. Recently, the anti-inflammatory activity of some antibacterial agents has also been suspected. Of these duel-action drugs, ansamycins represent an interesting family. Although their therapeutic use is restricted to potentially infectious inflammatory diseases, many experimental data suggest that these drugs also possess direct inhibitory activity on some crucial proinflammatory effectors. To date, the potent antimycobacterial activity of the therapeutically useful ansamycins precludes their widespread use in inflammatory diseases. However, biosynthetic manipulation remains an attractive route for the generation of pharmacologically useful analogs.