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WOMEN'S HEALTH

Pathophysiology of Mifepristone-Induced Septic Shock Due to Clostridium sordellii

Associate Professor Emeritus, Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown Medical School, Brown University, 174 Meeting St., Providence, RI 02912-9107, fax 401/863-1595, Ralph_Miech{at}brown.edu

Reprints: Dr. Miech

OBJECTIVE: To explain the role of mifepristone in medical abortions that results in fulminant and lethal septic shock due to Clostridium sordellii.

DATA SOURCES: MEDLINE, PubMed, and Google Scholar databases were searched (1984-March 2005). Key search terms were mifepristone, RU38486, RU486, Mifeprex, medical abortion, septic shock, innate immune system, cytokines, and Clostridium sordellii.

STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for the information related to the development of the understanding of the pathophysiology of mifepristone-induced septic shock due to C. sordellii.

DATA SYNTHESIS: The mechanisms of action of mifepristone were incorporated into the pathophysiology of septic shock due to C. sordellii. Mifepristone, by blocking both progesterone and glucocorticoid receptors, interferes with the controlled release and functioning of cortisol and cytokines. Failure of physiologically controlled cortisol and cytokine responses results in an impaired innate immune system that results in disintegration of the body's defense system necessary to prevent the endometrial spread of C. sordellii infection. The abnormal cortisol and cytokine responses due to mifepristone coupled to the release of potent exotoxins and an endotoxin from C. sordellii are the major contributors to the rapid development of lethal septic shock.

CONCLUSIONS: Theoretically, it appears that the mechanisms of mifepristone action favor the development of infection that leads to septic shock and intensifies the actions of multiple inflammatory cytokines, resulting in fulminant, lethal septic shock.

Key Words: abortion, Clostridium sordellii, mifepristone, septic shock

Published Online, July 26, 2005. www.theannals.com, DOI 10.1345/aph.1G189

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