The role of tumor necrosis factor-receptors in pregnancy with normal and adverse outcome

Jean Calleja-Agius¹, Shanthi Muttukrishna², Eric Jauniaux^1
1Academic Department of Obstetrics and Gynaecology, University College London Institute for Women's Health, WC1E 6HX London, United Kingdom; ²Anu Research Centre, University College Cork, Department of Obstetrics and Gynaecology, Fifth Floor, Cork University Maternity Hospital, Wilton, Cork, Republic of Ireland

Abstract: TNFα receptors, TNF-R1 and TNF-R2, mediate the biological activities of the multifunctional cytokine, tumor necrosis factor alpha, TNFα. These receptors have a central role in human pregnancy. Although each receptor induces distinct intracellular signals, they also have co-operative and overlapping effects. The membrane bound TNF-R1 carries out most of the pro-inflammatory activities of TNFα, especially those that are rapid, while TNF-R2 is involved in the late long-term effects of this cytokine. The soluble forms of these receptors can bind to TNFα, neutralizing its effects. In normal human pregnancy, TNFα receptors are present in the maternal circulation, placenta, amniotic fluid, and coelomic cavity. Changes in TNFα and its receptors are associated with adverse pregnancy outcomes, including miscarriage, preterm labor and preeclampsia. Advances in anti-TNFα therapy may have potential use in the management of complicated pregnancies.

Keywords: TNFα receptors, pregnancy, miscarriage, preeclampsia, preterm labor