Infant cortisol stress–response is associated with thymic function and vaccine response

Stress can impair T cell-mediated immunity. To determine if infants with high stress responses had deficits in T-cell mediated immunity, we examined the association of pain-induced cortisol responsiveness with thymic function and vaccine responses in infants. This study was performed among 306 (male = 153 and female = 153) participants of a randomized, controlled trial examining the effect of neonatal vitamin A supplementation on immune function in Bangladesh (NCT01583972). Salivary cortisol was measured before and 20 min after a needle stick (vaccination) at 6 weeks of age. The thymic index (TI) was determined by ultrasonography at 1, 6, 10 and 15 weeks. T-cell receptor excision circle and blood T-cell concentrations were measured at 6 and 15 weeks. Responses to Bacillus Calmette–Guérin (BCG), tetanus toxoid, hepatitis B virus and oral poliovirus vaccination were assayed at 6 and 15 weeks. Cortisol responsiveness was negatively associated with TI at all ages (p p = .0035) and 15 weeks (p = .0083), and was negatively associated with the delayed-type hypersensitivity (DTH) skin test response to BCG vaccination at 15 weeks (p = .034) in both sexes. Infants with a higher cortisol response to pain have differences in the T-cell compartment and a lower DTH response to vaccination. Sex differences in the immune system were seen as early as 6 weeks of age in these healthy infants.

应激可损害T细胞介导的免疫（T cell-mediated immunity）功能。为明确高应激应答婴儿是否存在T细胞介导的免疫功能缺陷，本研究探讨了婴儿疼痛诱导的皮质醇反应性与胸腺功能及疫苗应答之间的关联。本研究的306名研究对象（男、女各153名）来自一项在孟加拉国开展的评估新生儿维生素A补充对免疫功能影响的随机对照试验（NCT01583972）。在婴儿6周龄时，于针刺（疫苗接种）前及接种后20分钟检测其唾液皮质醇水平；分别于1、6、10和15周龄时通过超声检查测定胸腺指数（thymic index, TI）；分别于6和15周龄时检测T细胞受体切除环（T-cell receptor excision circle, TREC）及外周血T细胞浓度；分别于6和15周龄时检测婴儿对卡介苗（Bacillus Calmette–Guérin, BCG）、破伤风类毒素、乙型肝炎病毒疫苗及口服脊髓灰质炎疫苗的免疫应答。皮质醇反应性与各年龄点的胸腺指数均呈负相关（1周龄时p<0.0001，6周龄时p=0.0035，10周龄时p=0.0057，15周龄时p=0.0083）；且在两性中，15周龄时皮质醇反应性与卡介苗接种后的延迟型超敏反应（delayed-type hypersensitivity, DTH）皮肤试验应答均呈负相关（p=0.034）。疼痛诱导皮质醇应答更高的婴儿，其T细胞亚群存在异常，且疫苗接种后的DTH应答更低。在这些健康婴儿中，免疫系统的性别差异早在6周龄时即可显现。