The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding

Abstract

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Keywords: TNF-α; anti-TNF-α; breastfeeding; fertility; placental transfer; pregnancy; procreation.

Figure 1

Structure and nomenclature of tumor necrosis factor-alpha (TNF-α) inhibitors.

Figure 1

Structure and nomenclature of tumor necrosis factor-alpha (TNF-α) inhibitors.

Figure 2

The neonatal Fc receptor (FnRn) mediates the perinatal transfer of IgG. In humans, the neonatal Fc receptor for IgG (FcRn) binds maternal IgG in an acidic environment, transcytoses is across a polarized epithelial-cell barrier and releases a physiological pH. In humans, maternal-fetal IgG transfer occurs across the syncytiotrophoblast of the placenta. FcRn is expressed in the internal vesicles of the syncytiotrophoblast. On acidification in the endosome, FcRn binds to maternal IgG and transcytoses it to the fetal circulation where it is released as physiological pH.