Jain R, Zwickler D, Hollander C S, Brand H, Saperstein A, Hutchinson B, Brown C, Audhya T
Department of Medicine, New York University Medical Center, New York 10016.
Endocrinology. 1991 Mar;128(3):1329-36. doi: 10.1210/endo-128-3-1329.
We examined the role of CRF, a key mediator of the endocrine response to stress, in modulating immunosuppression during the subacute stress of intermittent electrical shock over 1 h. Administration of shock to intact rats resulted in a 74% decrement in T-lymphocyte proliferation and a 59% decrease in natural killer cytotoxicity. Similar suppression of these two parameters of immune function in response to shock was noted in adrenalectomized rats as well. The immunosuppressive effects of this shock were significantly and comparably blunted when both intact and adrenalectomized animals were pretreated 1) iv with either a highly potent polyclonal CRF antibody or a specific CRF antagonist or 2) intracerebroventricularly with either a high affinity monoclonal antibody to CRF or a specific CRF antagonist. An immunomodulatory role for CRF is further supported by the findings that administration of exogenous CRF, either iv (10 micrograms/animal) or intracerebroventricularly (1 microgram/animal), resulted in significant decrements in lymphocyte proliferation and natural killer cytotoxicity, similar to those seen with the stress paradigm. Our observations indicate that CRF plays a significant role in modulating the immune response to subacute stress, largely by adrenal-independent mechanisms.
我们研究了促肾上腺皮质激素释放因子（CRF）在调节间歇性电击1小时亚急性应激期间免疫抑制中的作用，CRF是对应激的内分泌反应的关键介质。对完整大鼠施加电击导致T淋巴细胞增殖减少74%，自然杀伤细胞细胞毒性降低59%。在肾上腺切除的大鼠中也观察到对电击的这两个免疫功能参数的类似抑制。当完整和肾上腺切除的动物在以下情况下进行预处理时，这种电击的免疫抑制作用会显著且同等程度地减弱：1）静脉注射高效多克隆CRF抗体或特异性CRF拮抗剂；2）脑室内注射针对CRF的高亲和力单克隆抗体或特异性CRF拮抗剂。外源性CRF的给药，无论是静脉注射（10微克/只动物）还是脑室内注射（1微克/只动物），都会导致淋巴细胞增殖和自然杀伤细胞细胞毒性显著降低，类似于在应激模式中观察到的情况，这一发现进一步支持了CRF的免疫调节作用。我们的观察结果表明，CRF在调节对亚急性应激的免疫反应中起重要作用，主要通过不依赖肾上腺的机制。
