Department of Cellular and Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Brain Behav Immun. 2012 Mar;26(3):439-50. doi: 10.1016/j.bbi.2011.11.005. Epub 2011 Dec 1.
Prenatal alcohol exposure (PAE) has adverse effects on the development of numerous physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system. HPA hyper-responsiveness and impairments in immune competence have been demonstrated. The present study investigated immune function in PAE females utilizing an adjuvant-induced arthritis (AA) model, widely used as a model of human rheumatoid arthritis. Given the effects of PAE on HPA and immune function, and the known interaction between HPA and immune systems in arthritis, we hypothesized that PAE females would have heightened autoimmune responses, resulting in increased severity of arthritis, compared to controls, and that altered HPA activity might play a role in the immune system changes observed. The data demonstrate, for the first time, an adverse effect of PAE on the course and severity of AA in adulthood, indicating an important long-term alteration in functional immune status. Although overall, across prenatal treatments, adjuvant-injected animals gained less weight, and exhibited decreased thymus and increased adrenal weights, and increased basal levels of corticosterone and adrenocorticotropin, PAE females had a more prolonged course of disease and greater severity of inflammation compared to controls. In addition, PAE females exhibited blunted lymphocyte proliferative responses to concanavalin A and a greater increase in basal ACTH levels compared to controls during the induction phase, before any clinical signs of disease were apparent. These data suggest that prenatal alcohol exposure has both direct and indirect effects on inflammatory processes, altering both immune and HPA function, and likely, the normal interactions between these systems.
产前酒精暴露 (PAE) 对许多生理系统的发育都有不良影响，包括下丘脑-垂体-肾上腺 (HPA) 轴和免疫系统。已经证明 HPA 过度反应和免疫功能受损。本研究利用佐剂诱导关节炎 (AA) 模型研究了 PAE 雌性的免疫功能，该模型广泛用于人类类风湿关节炎的模型。鉴于 PAE 对 HPA 和免疫功能的影响，以及 HPA 和免疫系统在关节炎中的已知相互作用，我们假设与对照组相比，PAE 雌性会产生更高的自身免疫反应，导致关节炎的严重程度增加，并且改变的 HPA 活性可能在观察到的免疫系统变化中起作用。该数据首次表明，PAE 对成年 AA 的病程和严重程度有不利影响，表明功能性免疫状态的重要长期改变。尽管总体而言，在整个产前处理中，佐剂注射动物体重增加较少，胸腺重量减少，肾上腺重量增加，基础皮质酮和促肾上腺皮质激素水平升高，但与对照组相比，PAE 雌性的疾病病程更长，炎症更严重。此外，与对照组相比，在诱导阶段（在出现任何疾病临床症状之前），PAE 雌性对刀豆蛋白 A 的淋巴细胞增殖反应减弱，基础 ACTH 水平升高更大。这些数据表明，产前酒精暴露对炎症过程既有直接影响，也有间接影响，改变了免疫和 HPA 功能，可能改变了这些系统之间的正常相互作用。
