Rifamycin SV Anti-inflammatory and Immunomodulatory Activities for Treatment of Mucosal and Liver Inflammation

Rifamycin SV (rifamycin), is a member of the ansamycin family of antimicrobial compounds which kills bacteria commonly associated with infectious diarrhea and other enteric infections. For colonic diseases like diverticulitis, inflammatory bowel syndrome (IBS) or inflammatory bowel disease (IBD), bacterial proliferation or microbial dysbiosis is associated with a strong inflammatory component. This inflammation has a profound influence on the liver via the gut-liver axis. This review summarizes the anti-inflammatory activities of rifamycin based on analyses of its impact on two key regulators of inflammation: PXR and NFκB. Rifamycin was found to activate PXR and two of its downstream targets, CYP3A4 and PgP, in liver and intestinal cell lines. Rifamycin also directly inhibited NFκB in a cell line which lacks PXR expression. These dual activities likely explain the inhibition of pro-inflammatory cytokine secretion from human colonic cells lines and activated CD4+ T cells. These experimental data define the immune regulatory characteristics of rifamycin and an emerging role in the treatment of both gastrointestinal (GI) and liver disorders.