Pro-inflammatory Cytokines in Animal and Human Gestation

Luana      Paulesu; Jayonta      Bhattacharjee; Nicoletta      Bechi; Roberta      Romagnoli; Silke      Jantra; Francesca      Ietta

doi:10.2174/138161210793797933

Abstract

The story of cytokines in pregnancy began about 30 years ago, approximately in concomitance with the understanding that cytokines are autocrine-paracrine regulators of physiological processes. Pro-inflammatory cytokines are predominant in the early and late events of gestation, e.g. pregnancy establishment and parturition, both of which have been described as inflammatory-like events. Proinflammatory cytokines are also produced in response to microbes constantly in contact with the female reproductive tract. While a proinflammatory response is beneficial to successful pregnancy, an exaggerated response, as may occur for an unresolved infection, could result in an unfavorable pregnancy outcome in animals and humans. Therapeutic strategies are required to avoid the risks to the health of fetus and mother. In this review, we discuss the involvement of pro-inflammatory cytokines in pregnancy at implantation and parturition, including the pathologies which might be related to an alteration of the cytokine levels. We also deal with the use of anti-cytokines and/or anti-inflammatory mediators to antagonize the action of pro-inflammatory cytokines. Finally we discuss the potential of animal models to evaluate the association of cytokines in the establishment and maintenance of pregnancy.

Keywords: Cytokine, pregnancy, maternal-fetal immunotolerance, implantation, labor, pregnancy disorders, Pro-inflammatory Cytokines, Human Gestation, autocrine-paracrine regulators, paracrine regulators, murine placenta, inflammation, immunosuppression, pre-eclampsia, interferons, interleukins, leukemia inhibitory factor, tumor necrosis factor, transforming growth factors, colony stimulating factors, vascular endothelial growth factors, pleiotropism, redundancy, synergism, mutual antagonism, GM-CSF, Th1/Th2 cytokine dichotomy, myometrium, uterine epithelial cells, estradiol, LPS-activated monocytes, immune response, endocrine disruptors, Macrophage migration inhibitory factor, Interleukin-1, COX-2, intracytoplasmic domain, 11-hydroxysteroid dehydrogenase, post-natal hypertension