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Pregnancy is a successful allograft, where fetal survival depends on the protection from maternal immune system attack. Maintaining an immune balance is crucial for a healthy pregnancy. To avoid recurrent spontaneous abortion (RSA), a fine-tuning of a complex immune network is required at the maternal-fetal interface, where one of the key mechanisms is the regulation of interacting cytokines in the mother. Cytokines play a role in all stages of physiological development from early embryonic growth to implantation and beyond. They also serve a critical function in maintaining pregnancy, stabilizing the immune environment, initiating labor, and facilitating delivery. Research into reproductive immunity has revealed that the etiology of RSA is closely related to the imbalance of immune cells and cytokines such as Th1 and Th2.
Figure 1. The polarization of macrophages and their characteristics. (Zhao Q Y, et al., 2022)
Th1 secretes cytokines, including IL-2, IL-12, TNF-α, and IFN-γ, to mediate cellular immune responses. The optimal concentration of Th1 cytokines during the early stage fosters angiogenesis during implantation and induces apoptosis in trophoblast cells, leading to maternal hypercoagulability and ultimately, miscarriage. On the other hand, Th2 cells secrete cytokines, including IL-4, IL-5, IL-10, and IL-13, which promote maternal and fetal immune tolerance while reducing the cytotoxicity of Th1 cells on embryonic trophoblast cells. During a typical pregnancy, the Th2-mediated immune response generally dominates the Th1/Th2 immune response, promoting maternal-fetal immune tolerance. However, in patients with RSA, the Th1-type immune response is often dominant.
IL-4 is a cytokine that promotes the differentiation of Th2 cells and inhibits the differentiation of Th1 cells, contributing to the maintenance of pregnancy.
IL-6 is a polymorphic cytokine that plays a role in inflammation, hematopoiesis, and immune regulation. It is involved in implantation, placentation, and labor.
IL-10 acts as an anti-inflammatory cytokine and plays a key role in the maintenance of pregnancy by suppressing the maternal immune response to the fetus.
TNF-α is a class of pro-inflammatory cytokines that play a role in implantation, placentation, and labor.
TGF-β acts as a multifunctional cytokine that plays a role in immunomodulation, inflammation, and tissue repair. It is involved in implantation, placenta, and fetal growth.
Creative BioMart takes the research into reproductive diseases further by offering a high-quality range of GMP cytokines, peptides, and proteins as well as customization services. If you are interested in our products or services, please contact us.
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