The stress of birth enhances in vitro spontaneous and IL‐8‐induced neutrophil chemotaxis in the human newborn

Abstract

The birth process induces fetal stress. Stress has profound effects on the immune system, also by acting on the trafficking of leukocytes, a process in which adhesion and chemotaxis are primordial and critical events for the development of effective antimicrobial defenses. The newborn is rapidly challenged by a microflora at the epithelia linings and therefore depending on early, innate immunity onset. The objective of the study was to investigate the immune response in cord blood from newborns in relation to different degrees of fetal stress, with focus on neutrophil chemotaxis. We analyzed in vitro transmigration ability of neutrophils and their CD11b expression, measured total white blood count (WBC) and the major leukocyte populations, interleukin (IL)-8, interferon (IFN)-gamma, and soluble E-Selectin, as well as relevant immuno-modulating hormones in infants born at term after Cesarean section prior to the start of labor (n = 55), normal vaginal delivery (n = 87), and assisted delivery (n = 26). Arterial pH and lactate were used as stress markers. We found that spontaneous and IL-8-induced transmigration ability of neutrophils from newborns after normal delivery was significantly higher compared with that of neutrophils from Cesarean section or from adults. With a progressive increase in fetal stress, there were significant elevations in total WBC, in particular neutrophils and monocytes, as well as an enhanced IL-8 and soluble E-Selectin level. Assisted delivery, associated with the highest degree of fetal stress in addition had an enhanced lymphocyte and monocytes count as well as an increased IFN-gamma level. There were significant direct correlations between neutrophils and monocytes, respectively, with cortisol, beta-endorphin, and prolactin. Interferon-gamma was directly related to dopamine, as well as to the lymphocyte and monocyte count. The setting of the HPA-axis at birth is a promoter of an alarm response and a surge of neuroendocrine immuno-modulating factors that enhances antimicrobial defenses of the newborn. We speculate that IL-8 induced by normal labor may be a priming factor for an increased neutrophil chemotaxis through the pre-activated endothelium of the fetus. Assisted delivery may trigger excessive recruitment of additional inflammatory cells and IFN-gamma release.

Differential neutrophil chemotactic response towards IL-8 and bacterial N-formyl peptides in term newborn infants

“…Blood was collected from the placental side of the umbilical cord immediately after elective cesarean section was performed under spinal anesthesia. Since neutrophil activity is increased due to fetal stress in newborn infants during vaginal delivery (18,19), we studied neutrophils from the umbilical cord of healthy term newborn infants, immediately after elective cesarean section. Peripheral blood was collected from healthy adults ( n  = 8), aged 18–65 years old.…”

Does the maternal vaginal microbiota play a role in seeding the microbiota of neonatal gut and nose?

“…There is emerging evidence that lack of vaginal delivery, and in particular of labour, may interfere with the maturation of immune cells and may change the levels of circulating cytokines (Almanzar et al, 2015;Thysen et al, 2015). Delivery mode has differential consequences for activation of the foetal hypothalamic-pituitary-adrenal axis, with profound effects on the developing foetal immune system (Yektaei-Karin et al, 2007). Small differences in the perinatal environment can result in considerable differences in gut microbiota of the neonate.…”

Less Neutrophil Extracellular Trap Formation in Term Newborns than in Adults

“…These data suggest that neonatal NET formation depends also on the type of stimulation. Although we did not study bacterial killing, we used fMLP as a stimulus, which mimics the N-formyl oligopeptides released by bacteria and activates circulating blood leukocytes by binding to specific G protein-coupled receptors on these cells [22]. We also used LPS, which simulates pathological stimulation by signaling via TLR2/TLR4 [23].…”