immunology of unexplained recurrent spontaneous abortion: Cytokines as key mediators

ABSTRACT

Spontaneous abortion is one of the most common complications of pregnancy. Recurrent spontaneous abortion [RSA], defined as the occurrence of three consecutive abortions, occurs due to several identifiable causes such as anatomic, genetic, endocrinologic and infectious etiologies, but a substantial proportion of RSA, up to 50-60%, are due to unexplained or unknown etiologies. Of the various humoral immune etiologies that have been investigated, only anti-phospholipid antibodies have been confirmed as being etiologic factors, but that too, in a small proportion of the cases of RSA. Cellular immune effectors and cytokines have been the focus of intense investigation recently, and it appears that certain cytokines may be beneficial to pregnancy, while some are actually antagonistic to pregnancy. This article reviews recent observations on the association between cytokines and unexplained recurrent spontaneous abortion. Evidence from studies on murine and human pregnancy points to a strong association between maternal Th2-type immunity and successful pregnancy on the one hand and between Th1-type immune reactivity and pregnancy loss on the other. While there is a paucity of data from human pregnancy indicating that Th1-type immune effectors actually lead to pregnancy, it is difficult to ignore the compelling evidence linking inappropriate Th1-type immunity to pregnancy loss. Th2-type immunity may play protective roles during pregnancy, hence the nexus between a Th2 shift and successful pregnancy. This article examines these associations and discusses possible mechanisms underlying immunologically- mediated pregnancy failure