Disruption of the innate immune system by mifepristone and lethal toxin of Clostridium sordellii

The innate immune system is an immediate host response system for combating invading bacteria by initiating a protective local tissue inflammatory response. Pattern recognition molecules that are uniquely expressed in bacteria activate the host's Toll-like receptors to produce cytokines in the form of the pro-inflammatory chemokines and interleukins. If the synthesis of pro-inflammatory cytokines is not properly controlled by cortisol, pro-inflammatory cytokines gain access to the systemic circulation and result in a systemic cytokine storm that is responsible for initiating septic shock and multiple organ dysfunctions. Cortisol-activated glucocorticoid receptors result in the synthesis and release of the anti-inflammatory cytokine interleukin-10, which prevents the further synthesis of pro-inflammatory cytokines. During a mifepristone-induced abortion, the blockade of glucocorticoid receptors by mifepristone results in the disruption of the innate immune system. The combination of ischemic decidua, necrotic products of conception and a disrupted innate immune system sets the stage for an infection with anaerobic Clostridium sordellii which secretes a lethal toxin that irreversibly inactivates guanosine triphosphate synthase of phagocytes to further compromise the innate immune system. Mifepristone-induced necrotic tissue, blockade of glucocorticoid receptors by mifepristone producing a cytokine storm and secretion of lethal toxin by Clostridium sordellii leads to fulminating lethal multiple organ dysfunctions.