The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia

Abstract

Pregnancy can be defined a vascular event upon endocrine control. In the human hemo-chorial placentation the chorionic villi penetrate the wall of the uterine spiral arteries, to provide increasing amounts of nutrients and oxygen for optimal fetal growth. In any physiological pregnancy the natural maternal response is of a Th1 inflammatory type, aimed at avoiding blood loss through the arteriolar wall openings. The control of the vascular function, during gestation as in any other condition, is achieved through the action of two main types of prostanoids: prostaglandin E2 and thromboxane on the one hand (for vasoconstriction and coagulation), prostacyclin on the other (for vasodilation and blood fluidification). The control of the maternal immune response is upon the responsibility of the fetus itself. Indeed, the chorionic villi are able to counteract the natural maternal response, thus changing the inflammatory Th1 type into the anti-inflammatory Th2. Clinical and experimental research in the past half century address to inflammation as the leading cause of abortion, pregnancy loss, premature delivery and related pulmonary, cerebral, intestinal fetal syndromes. Increased level of Interleukin 6, Interleukin 1-beta, Tumor Necrosis Factor-alfa, Interferon-gamma, are some among the well-known markers of gestational inflammation. On the other side, COVID-19 pneumonia is a result of extensive inflammation induced by viral replication within the cells of the respiratory tract. As it may happen in the uterine arteries in the absence of an effective fetal control, viral pneumonia triggers pulmonary vascular coagulation. The cytokines involved in the process are the same as those in gestational inflammation. As the fetus breathes throughout the placenta, fetal death from placental thrombosis is similar to adult death from pulmonary thrombosis. Preventing and counteracting inflammation is mandatory in both conditions. The most relevant literature dealing with the above-mentioned concepts is reviewed in the present article.

SARS-CoV-2 variant-related abnormalities detected by prenatal MRI: a prospective case–control study

“…This may be at least partially explained by the presence of a large number of immune cells in the placental tissue: In the gestational decidua, large numbers of macrophages, natural killer (NK) cells, and dendritic cells infiltrate the decidua during the first trimester and cluster around the invading trophoblast cells. 31 …”

Mitochondrial ROS Accumulation Contributes to Maternal Hypertension and Impaired Remodeling of Spiral Artery but Not IUGR in a Rat PE Model Caused by Maternal Glucocorticoid Exposure

“…Thus, increased circulatory PGE2 levels could increase systemic levels of Il1b and Tnf-α in DEX rats. Although pregnancy is considered a state of low-grade, systemic inflammatory responses [60,61], increased circulatory levels of inflammatory factors including Il1b, Il6, and Tnf-α are associated with adverse pregnancy outcomes, such as PE [62][63][64][65][66]. In addition, inflammatory factors promote the production of antiangiogenic factors sFlt-1 and sEng in placenta [67][68][69].…”

Placental Characteristics of a Large Italian Cohort of SARS-CoV-2-Positive Pregnant Women

“…Moreover, most of the placentas showing CA and/or F (170/404; 42.3%) involved women with a diagnosis of SARS-CoV-2 within 7 days of delivery. This result may suggest a possible involvement of SARS-CoV-2, considering the cytokine storm that this virus may induce, such as tumour necrosis factor (TNFa), interferon γ (INFγ), interleukin-6 (IL6), interleukin- 1b (IL1b), and chemokines such as monocyte chemoattractant protein-1 (MCP-1/CCL2), which can also favour granulocyte stimulation [ 21 , 22 , 23 ]. CA is expected to occur around 10–20% of the time in non-COVID pregnancies [ 24 ].…”