Shurin M R, Kusnecov A W, Riechman S E, Rabin B S
Department of Pathology, University of Pittsburgh Medical Center, PA 15213, USA.
Psychoneuroendocrinology. 1995;20(8):837-49. doi: 10.1016/0306-4530(95)00010-0.
In the present study we investigated the effect of a brief exposure (15 s) to a conditioned aversive stimulus (CS) on the proliferative response of spleen and peripheral blood lymphocytes (PBL) in Lewis, Fischer 344 and Sprague-Dawley rats. Plasma levels of ACTH and corticosterone were also measured. For conditioning, rats were exposed to 10 presentations of a 5 s duration foot-shock (1.6 mA) preceded by a 15 s tone. Seven days later, animals were exposed to the auditory signal without electric shock. Significant differences were found in both the kinetics and the magnitude of altered mitogenic responsiveness of PBL between the different strains of rats. Enhancement of PBL responsiveness to mitogens was observed in Fischer and Sprague-Dawley rats immediately after exposure to the CS. A significant decrease in the response of PBL to mitogens was found in Lewis and Sprague-Dawley rats 10 min after exposure to the CS. The PBL response of Sprague-Dawley and Fischer rats returned to baseline at 30 min, but not in Lewis rats. Proliferative activity of spleen lymphocytes in response to the CS was suppressed from baseline in all rat strains, but the timing and degree of suppression differed. Fischer rats had the largest percentage of suppression. The earliest suppression of spleen mitogenic function after exposure to the CS was in Fischer rats, while the Lewis rats had the latest onset of suppression, with the Sprague-Dawley rats being intermediate. Plasma levels of ACTH and corticosterone peaked at 10 min in all strains of rats. The magnitude of hormonal elevation differed in the different rat strains, suggesting that corticosterone may not have a variable immunomodulatory role in each strain. These data suggest that a brief psychological stressor results in activation of the HPA axis and is associated with strain-dependent alterations of lymphocyte responsiveness to non-specific mitogens. The short-term exposure to a CS which produces different parameters of lymphocyte functional modulation, provides a useful tool to study the mechanisms of stressor-induced immune alteration.
在本研究中，我们调查了对Lewis、Fischer 344和Sprague-Dawley大鼠短暂暴露（15秒）于条件性厌恶刺激（CS）对脾脏和外周血淋巴细胞（PBL）增殖反应的影响。还测量了促肾上腺皮质激素（ACTH）和皮质酮的血浆水平。为了进行条件反射训练，大鼠先接受10次时长5秒（1.6毫安）的足部电击，电击前有15秒的音调提示。七天后，让动物暴露于听觉信号但无电击。在不同品系大鼠中，PBL有丝分裂反应性改变的动力学和幅度均存在显著差异。在Fischer和Sprague-Dawley大鼠中，暴露于CS后立即观察到PBL对有丝分裂原反应性增强。在Lewis和Sprague-Dawley大鼠中，暴露于CS 10分钟后发现PBL对有丝分裂原的反应显著降低。Sprague-Dawley和Fischer大鼠的PBL反应在30分钟时恢复到基线水平，但Lewis大鼠未恢复。所有品系大鼠脾脏淋巴细胞对CS的增殖活性均从基线水平受到抑制，但抑制的时间和程度不同。Fischer大鼠的抑制百分比最大。暴露于CS后，Fischer大鼠脾脏有丝分裂功能最早受到抑制，而Lewis大鼠抑制开始最晚，Sprague-Dawley大鼠介于两者之间。所有品系大鼠的ACTH和皮质酮血浆水平在10分钟时达到峰值。不同品系大鼠激素升高的幅度不同，表明皮质酮在每个品系中可能没有可变的免疫调节作用。这些数据表明，短暂的心理应激源会导致下丘脑-垂体-肾上腺（HPA）轴激活，并与淋巴细胞对非特异性有丝分裂原反应性的品系依赖性改变有关。对CS的短期暴露产生不同的淋巴细胞功能调节参数，为研究应激源诱导的免疫改变机制提供了一个有用的工具。
