Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure

Abstract

The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8–12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health.

Adverse health outcomes associated with fetal alcohol exposure: A systematic review focused on immune‐related outcomes

“…Notably, preclinical research has demonstrated that both peripheral and central cytokines as well as C‐reactive protein (CRP), a marker of inflammation, were altered in female rat offspring with PAE. Specifically, animals showed increased pro‐inflammatory cytokines in serum, hippocampus, and prefrontal cortex and decreased levels in the spleen and hypothalamus and increased serum CRP . The authors suggested that the lower cytokine levels in the spleen, an important immune organ, and the hypothalamus, an important integrator of immune and endocrine responses, may underlie the increased susceptibility to infection.…”

“…Furthermore, Raineki et al found that exposure to early‐life adversity differentially impacted the immune system of offspring with PAE compared to controls, such that offspring with PAE showed a lack of responsivity to early‐life adversity. The authors suggested that PAE alters the development of the immune system, leading to inappropriate immune system responses that may be displayed when the system is challenged later in life.…”

“…33 There was also evidence that altered immune responses were transient, with pre-weanling, juvenile or adolescent PAE offspring exhibiting alterations that were normalized by adulthood. 29,[34][35][36][37] There was also some evidence for alterations to the humoral immune response, with changes in peripheral or central cytokine production, [38][39][40] although other studies reported no change. 41 Finally, studies examining LPS-and cytokineinduced fever in adult rats 42,43 found an attenuated febrile response in PAE offspring, with the authors suggesting that this may also contribute to the decreased resistance to infection observed in animals and humans following PAE.…”

“…18 These studies were conducted in children of different ethnicities, and consequently, this is an area that requires further research in However, it is also important to consider that although infection outcomes were not documented, previous research has suggested that low levels of PAE may underlie susceptibility to the development of autoimmune diseases through dysregulated cytokine production. 44 Notably, preclinical research has demonstrated that both peripheral and central cytokines 8 as well as C-reactive protein (CRP), 39 a marker of inflammation, were altered in female rat offspring with PAE. Specifically, animals showed increased pro-inflammatory cytokines in serum, hippocampus, and prefrontal cortex and decreased levels in the spleen and hypothalamus 8 and increased serum CRP.…”

“…Specifically, animals showed increased pro-inflammatory cytokines in serum, hippocampus, and prefrontal cortex and decreased levels in the spleen and hypothalamus 8 and increased serum CRP. 39 The authors suggested that the lower cytokine levels in the spleen, an important immune organ, and the hypothalamus, an important integrator of immune and endocrine responses, may underlie the increased susceptibility to infection.…”