This theory postulates that pregnancy is an anti-inflammatory condition23–25 and a shift in the type of cytokines produced would

MLN0128 molecular weight lead to abortion or pregnancy complications. While many studies confirmed this hypothesis, a similar number of studies argued against this notion.19 The reason for these contradictory results may be owing to oversimplification of disparate observations made during pregnancy. In the aforementioned studies, pregnancy was evaluated as a single event, when in reality it has three distinct immunological phases that are characterized by distinct biological processes and can be symbolized by how the pregnant woman feels.22,26 Implantation, placentation and the first and early second trimester of pregnancy resemble ‘an open wound’ that requires a strong inflammatory response. During this first stage, the blastocyst has to break through

the epithelial lining of the uterus to implant, damage the endometrial tissue Ceritinib ic50 to invade; followed by the trophoblast replacement of the endothelium and vascular smooth muscle of the maternal blood vessels to secure an adequate placental–fetal blood supply.27 All these activities create a veritable ‘battleground’ of invading cells, dying cells and repairing cells. An inflammatory environment is required to secure the adequate repair of the uterine epithelium and the removal of cellular debris. Meanwhile, the mother’s well-being is clinically affected: she feels sick because her whole body is struggling to adapt to the presence of the fetus (in addition to hormonal changes and other factors, this

inflammatory response is responsible for ‘morning sickness’). Thus, the first trimester Fenbendazole of pregnancy is a pro-inflammatory phase.28 The second immunological phase of pregnancy is, in many ways, the optimal time for the mother. This is a period of rapid fetal growth and development. The mother, placenta and fetus are symbiotic, and the predominant immunological feature is induction of an anti-inflammatory state. The woman no longer suffers from nausea and fever as she did in the first stage, in part because the immune response is no longer the predominant endocrine feature. Finally, during the last immunological phase of pregnancy, the fetus has completed its development; all the organs are functional and prepared for the external world. Now the mother needs to deliver the baby; this is achieved through renewed inflammation. Parturition is characterized by an influx of immune cells into the myometrium to promote recrudescence of an inflammatory process.29,30 This pro-inflammatory environment promotes the contraction of the uterus, expulsion of the baby and rejection of the placenta. In conclusion, pregnancy is a pro-inflammatory and anti-inflammatory condition, depending upon the stage of gestation.31,32 These differences in cytokines may also reflect the sensitivity to infectious diseases.