New generation contraceptives: interleukin 11 family cytokines as non-steroidal contraceptive targets.
In the 50 years since the introduction of the contraceptive pill there have been no significant breakthroughs in contraceptive technology. It is clear that the currently available contraceptives fail to meet world-wide requirements, particularly in developing countries, therefore new methods of contraception are highly desirable. Gene deletion studies in mice have identified that the two cytokines interleukin (IL) 11 and leukemia inhibitory factor (LIF) are absolutely required for embryo implantation. Studies have demonstrated that administration of long acting IL11 and LIF inhibitors blocks embryo implantation resulting in infertility in mice. Clinical studies reveal that both cytokines are important regulators of embryo implantation in humans. Preventing implantation by targeting endometrial IL11 and LIF may be useful as a pharmacological non-hormonal strategy for women. In addition, vaginal application of the IL11 or LIF inhibitor with microbicides that block sexually transmitted infections could act as dual-role contraceptives, preventing implantation and sexually transmitted infections.
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Melbourne 3168, Australia. evdokia.dimitriadis@princehenrys.org
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Menkhorst
D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology*; D000818:Animals; D002986:Clinical Trials as Topic; D003267:Contraception / Q000639:trends; D010064:Embryo Implantation / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D051379:Mice
D000020:Abortifacient Agents, Nonsteroidal; D017370:Interleukin-11; D053605:Leukemia Inhibitory Factor