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Psychological stress, cortisol, and B lymphocyte decrements

心理压力、皮质醇和 B 淋巴细胞减少

基本信息

批准号：
7282386
负责人：
Bonnie A McGregor
金额：
$ 8.4万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2009-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Cancer vaccines are emerging as important tools for cancer treatment and prevention. Unfortunately, the cohorts that ultimately will benefit most from the vaccines, those at elevated risk for cancer, are likely to be stressed. Chronic stress can impair immune function, including immune response to vaccines. An inadequate response to vaccines can weaken their protective effect ;1 however, the mechanism by which stress exerts its effect on vaccine response is not known. One mechanism may involve stress-related increases in cortisol leading to decrements in B lymphocyte number. B lymphocytes are important for vaccine response. The immune system responds to invading pathogens (and vaccines) with a well-orchestrated cascade of events that involve a variety of immune cells and ultimately result in the production of antibodies by mature plasma cells of the B lymphocyte lineage. Previous work by our group has shown that high levels of academic stress are associated with very low numbers of peripheral blood B lymphocytes. There is ample in vitro and in vivo evidence that high levels of glucocorticoids cause reductions in B lymphocytes in mice. There is ample evidence that high levels of stress are associated with elevated cortisol levels in humans, but the evidence regarding cortisol causing reductions in B lymphocytes in humans is limited. There are only in vitro data to suggest high levels of cortisol in bone marrow cultures are associated with reductions in early B lymphocytes. To our knowledge, there are no in vivo human studies reporting increases in cortisol due to psychological stress are associated with dramatic decrements in B lymphocyte number. The purpose of the present biobehavioral research is to fill this gap with a longitudinal study of the effects of academic stress on salivary cortisol and B lymphocyte number among 40 comparison participants and 40 students over the course of their first year of graduate school which culminates with the qualifying examinations. These data will provide excellent preliminary data to support a larger grant application studying psychological stress, cortisol, B lymphocyte number, and antibody response to vaccine. Relevance of the present research to public health: Cancer vaccines are emerging as important tools for cancer treatment and prevention. But psychological stress can impair immune response to vaccine, and the people who will benefit most from cancer vaccines, those at genetic risk for cancer, are likely to be stressed. The present study will begin to elucidate the mechanism by which psychological stress impairs immune response to vaccines.

描述(申请人提供)：癌症疫苗正在成为癌症治疗和预防的重要工具。不幸的是，最终将从疫苗中受益最大的人群，即癌症风险较高的人群，可能会受到压力。慢性压力会损害免疫功能，包括对疫苗的免疫反应。对疫苗的不充分反应会削弱疫苗的保护作用；1然而，应激对疫苗反应的影响机制尚不清楚。一种机制可能涉及与压力相关的皮质醇增加，导致B淋巴细胞数量减少。B淋巴细胞对疫苗的应答很重要。免疫系统对入侵的病原体(和疫苗)做出反应，通过一系列精心安排的事件，涉及各种免疫细胞，最终导致B淋巴细胞系的成熟浆细胞产生抗体。我们小组之前的工作表明，高水平的学习压力与非常低的外周血液B淋巴细胞数量有关。有大量的体外和体内证据表明，高水平的糖皮质激素会导致小鼠B淋巴细胞的减少。有充分的证据表明，高水平的压力与人类皮质醇水平升高有关，但关于皮质醇导致人类B淋巴细胞减少的证据有限。只有体外数据表明，骨髓培养中高水平的皮质醇与早期B淋巴细胞的减少有关。据我们所知，没有活体人体研究报告，由于心理压力导致的皮质醇增加与B淋巴细胞数量的急剧减少有关。这项生物行为研究的目的是通过纵向研究40名比较参与者和40名研究生在研究生一年级期间学习压力对唾液皮质醇和B淋巴细胞数量的影响来填补这一空白。这些数据将为研究心理应激、皮质醇、B淋巴细胞数量和对疫苗的抗体反应的更大的拨款申请提供极好的初步数据。本研究与公共卫生的相关性：癌症疫苗正在成为癌症治疗和预防的重要工具。但心理压力会削弱对疫苗的免疫反应，而那些将从癌症疫苗中受益最大的人，那些具有癌症遗传风险的人，可能会受到压力。本研究将开始阐明心理应激损害疫苗免疫反应的机制。