Immune Function in Offspring of Nonhuman Primates (<i>Macaca nemestrina</i>) Exposed Weekly to 1.8 g/kg Ethanol during Pregnancy: Preliminary Observations

Grossmann, Angelika; Sj, Astley; Hd, Liggitt; Sk, Clarren; Shiota, Faith; Kennedy, Bryan; Me, Thouless; Maggio‐Price, Lillian

doi:10.1111/j.1530-0277.1993.tb00848.x

Cited by 24 publications

(12 citation statements)

References 24 publications

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“…Cellular deficits in B cell development in the liver (Biber et al, 1998;Moscatello et al, 1999), depressed T cell development within the thymus (Grossmann et al, 1993;Jerrells and Weinberg, 1998;Redei et al, 1989), and alterations of lymphocyte subsets (Giberson et al, 1997;Wolcott et al, 1995) have been described in juvenile and adult animals prenatally exposed to ETOH. The current study provides further evidence that in utero ETOH also affects another developing immune cell, namely the resident alveolar macrophage in the term lung.…”

Section: Discussionmentioning

confidence: 98%

In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol Exposure

Ping

Harris

Brown

et al. 2007

Alcoholism Clin & Exp Res

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Background: The effects of in utero alcohol exposure on the immune function of the newborn remain under investigation. Fetal ethanol (ETOH) exposure increases oxidative stress in the developing lung, in part due to decreased availability of the antioxidant glutathione (GSH). We have previously shown that in utero ETOH impairs alveolar macrophage phagocytosis and viability in the premature pup, while maintaining GSH availability with maternal supplementation of S-adenosylmethionine (SAM) during ETOH ingestion improves macrophage function and viability. We hypothesized that dysfunction of the neonatal alveolar macrophage exposed to ETOH in utero would persist at term gestation.Methods: Using a guinea-pig model of fetal ETOH exposure, timed-pregnant guinea-pigs were pair-fed ETOH AE the GSH precursor SAM and the diet continued until spontaneous delivery. Term alveolar macrophages were evaluated using fluorescent microscopy for phagocytosis and apoptosis after in vitro incubation with Staphalococcus aureus. Using an in vivo model of intranasal Staph. aureus inoculation, the in vivo function of the term alveolar macrophage was also investigated using confocal fluorescent analysis.Results: In utero ETOH exposure increased oxidant stress in the alveolar macrophage and decreased phagocytosis and viability in vitro and in vivo. Confocal analysis of phagocytosis in vivo demonstrated a marked impairment of internalization of the bacteria by the ETOH-exposed alveolar macrophage. The addition of SAM during maternal ETOH ingestion prevented loss of alveolar macrophage function and viability in vitro and in vivo.Conclusions: In utero ETOH exposure impairs alveolar macrophage function and viability in vitro and in vivo even at term gestation. The ETOH-induced changes in macrophage function and viability can be ablated with maternal SAM supplementation. Further investigations are required to identify the mechanisms of ETOH-induced derangement of phagocytosis in the neonatal alveolar macrophage and the clinical ramifications of altered immune function after in utero alcohol exposure for the newborn.

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Section: Discussionmentioning

confidence: 98%

In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol Exposure

Ping

Harris

Brown

et al. 2007

Alcoholism Clin & Exp Res

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“…Furthermore, the altered immune function attributable to in utero alcohol exposure persists into childhood (25) and adulthood (42). Animal models of fetal ethanol exposure also suggest that immune system development is compromised, and this can persist into childhood and adulthood (7,17,24,36). A recent study found that mice prenatally exposed to ethanol exhibit enhanced disease severity when infected with influenza virus in adulthood, and more time was taken to clear the virus from lungs of ethanol-exposed than control mice (29).…”

Section: Immune Statusmentioning

confidence: 99%

Effects of prenatal ethanol exposure on the lungs of postnatal lambs

Sozo

Vela

Stokes

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Prenatal ethanol exposure increases collagen deposition and alters surfactant protein (SP) expression and immune status in lungs of near-term fetal sheep. Our objectives were to determine 1) whether these prenatal effects of repeated gestational ethanol exposure persist after birth and 2) whether surfactant phospholipid composition is altered following prenatal ethanol exposure. Pregnant ewes were chronically catheterized at 90 days of gestational age (DGA) and given a 1-h daily infusion of ethanol (0.75 g/kg, n = 9) or saline (n = 7) from 95 to 135 DGA; ethanol administration ceased after 135 DGA. Lambs were born naturally at full term (146 ± 0.5 DGA). Lung tissue was examined at 9 wk postnatal age for alterations in structure, SP expression, and inflammation; bronchoalveolar lavage fluid was examined for alterations in surfactant phospholipid composition. At 134 DGA, surfactant phospholipid concentration in amniotic fluid was significantly reduced (P < 0.05) by ethanol exposure, and the composition was altered. In postnatal lambs, there were no significant differences between treatment groups in birth weight, postnatal growth, blood gas parameters, and lung weight, volume, tissue fraction, mean linear intercept, collagen content, proinflammatory cytokine gene expression, and bronchoalveolar lavage fluid surfactant phospholipid composition. Although SP-A, SP-B, and SP-C mRNA levels were not significantly different between treatment groups, SP-D mRNA levels were significantly greater (P < 0.05) in ethanol-treated animals; as SP-D has immunomodulatory roles, innate immunity may be altered. The adverse effects of daily ethanol exposure during late gestation on the fetal lung do not persist to 2 mo after birth, indicating that the developing lung is capable of repair.

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“…Animal models of prenatal alcohol exposure (PAE) support and extend the clinical findings. Increased susceptibility to infections (Grossmann et al, 1993; McGill et al, 2009) and malignancies (Gottesfeld and Abel, 1991), deficits in immune organ development (Bray et al, 1993; Ewald and Frost, 1987; Ewald and Walden, 1988; Redei et al, 1989), decreased splenic lymphocyte, T lymphoblast, and B cell proliferative responses to stimulation (Gottesfeld et al, 1990; Jerrells and Weinberg, 1998; Weinberg and Jerrells, 1991; Wolcott et al, 1995), blunted LPS-induced febrile responses (Taylor et al, 1999), dampened cytokine responses to immune challenge (Chiappelli et al, 1997; Kim et al, 1999; Lee and Rivier, 1993), and a more severe and prolonged course of inflammation in an adjuvant-induced arthritis model (Zhang et al, 2012) have been reported in models of in utero alcohol exposure [reviewed in Bodnar and Weinberg 2013].…”

Section: Introductionmentioning

confidence: 99%

Evidence for an immune signature of prenatal alcohol exposure in female rats

Bodnar

Hill

Weinberg

2016

Brain, Behavior, and Immunity

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Evidence for immune/neuroimmune disturbances as a possible root cause of a range of disorders, including neurodevelopmental disorders, is growing. Although prenatal alcohol exposure (PAE) impacts immune function, few studies to date have examined immune function in relation to long-term negative health outcomes following PAE, and most have focused on males. To fill this gap, we utilized a rat model to examine the effects of PAE on immune/neuroimmune function during early-life [birth (postnatal day 1; P1), P8, and weaning (P22)] in PAE and control females. Due to the extensive interplay between the immune and endocrine systems, we also measured levels of corticosterone and corticosterone binding globulin (CBG). While corticosterone levels were not different among groups, CBG levels were lower in PAE offspring from P1–P8, suggesting a lower corticosterone reservoir that may underlie susceptibility to inflammation. Spleen weights were increased in PAE rats on P22, a marker of altered immune function. Moreover, we detected a unique cytokine profile in PAE compared to control offspring on P8 – higher levels in the PFC and hippocampus, and lower levels in the hypothalamus and spleen. The finding of a specific immune signature in PAE offspring during a sensitive developmental period has important implications for understanding the basis of long-term immune alterations and health outcomes in children with Fetal Alcohol Spectrum Disorder (FASD). Our findings also highlight the future possibility that immune-based intervention strategies could be considered as an adjunctive novel therapeutic approach for individuals with FASD.

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Immune Function in Offspring of Nonhuman Primates (Macaca nemestrina) Exposed Weekly to 1.8 g/kg Ethanol during Pregnancy: Preliminary Observations

Cited by 24 publications

References 24 publications

In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol Exposure

In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol Exposure

Effects of prenatal ethanol exposure on the lungs of postnatal lambs

Evidence for an immune signature of prenatal alcohol exposure in female rats

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