Altered Immune Function in Human Newborns after Prenatal Administration of Betamethasone: Enhanced Natural Killer Cell Activity and Decreased T Cell Proliferation in Cord Blood

Abstract

During the course of human pregnancy, glucocorticoid (GC) treatment is given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, in animal studies, a number of side effects of perinatal GC treatment have been described. The aim of the present study was to evaluate in humans the effects of antenatal GC treatment on development of the immune system. In addition, we examined the development of immune reactivity in infants born preterm and at term who did not receive GC treatment antenatally. We tested mitogen-induced T cell proliferation, natural killer cell activity, and lipopolysaccharide-induced IL-6 production in cord blood samples. We found that there is a significant effect of gestational age on the capacity of T cells to proliferate and of natural killer cells to kill K562 tumor cells. The capacity to produce IL-6 does not change between gestational age 26 and 41 wk. Moreover, our results show that antenatal treatment with GC does have immunomodulatory effects: T cell proliferation is decreased in infants born very preterm (gestational age 26-31 wk) as well as in infants born between 32 and 36 wk of gestation. In contrast, the activity of natural killer cells is only increased in GC-treated infants born between 26 and 31 wk. We did not observe a significant effect of antenatal GC treatment on the capacity to produce IL-6.

Exposure to a Dysfunctional Glucocorticoid Receptor from Early Embryonic Life Programs the Resistance to Experimental Autoimmune Encephalomyelitis Via Nitric Oxide-Induced Immunosuppression

“…These results may explain the difference in the susceptibility to inflammatory diseases depending on prenatal experiences known to influence the expression and function of GRs and may thus have clinical implications for the development of autoimmune diseases in humans (65). Modulation of iNOS/NO by stress-or pharmacologically induced alterations at the GR level may also have potential therapeutic implications for such autoimmune diseases.…”

Antenatal maternal corticosteroid administration and markers of oxidative stress and inflammation in umbilical cord blood from very low birth weight preterm newborn infants

“…Kavelaars et al 29 não encontraram supressão de síntese de IL-6 em células humanas de cordão umbilical de fetos a termo e pré-termo. No entanto, Kramer et al 9 , em trabalhos experimentais com neutrófilos de ovelhas pré-termo, demonstraram que a betametasona administrada à mãe produzia supressão na produção de IL-6 após 15 horas.…”

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3 - /CD56+16+) in umbilical cord blood than those without pre-eclampsia

“…Our finding that pre-eclampsia was associated with an increase in the proportion of NK cells in umbilical cord blood is in agreement with results reported by Darmochwal-Kolarz and colleagues 10 . However, our study population included preterm pre-eclamptic patients, and we took into account in the analysis the potential effect of labor 38,39 , maternal steroid administration 40 , type of anesthesia 41 and umbilical cord blood pH. Similarly, our observation that labor with vaginal delivery is associated with an increased NK cell percentage is consistent with previous studies that demonstrated a higher percentage of NK cells 38,39 and T lymphocytes expressing CD2, CD3 and CD4 in neonates born after labor than in those born by Cesarean section without labor.…”