Saphier D
Hadassah University Hospital, Department of Neurology, Jerusalem, Israel.
Psychoneuroendocrinology. 1989;14(1-2):63-87. doi: 10.1016/0306-4530(89)90056-5.
The studies presented herein demonstrate the potency with which activity of the immune system is able to influence the central nervous system. Electrophysiological recordings have demonstrated significant changes in preoptic area/anterior hypothalamic (PO/AH) multiunit electrical activity (MUA) following sensitization with sheep red blood cells. The peak of activity occurred on the fifth day after immunization, the same day that serum antibodies were first detected. A significant increase in paraventricular nucleus MUA was also demonstrated, but this appeared to be delayed with respect to that in the PO/AH, occurring on the sixth day. Further changes thought to be associated with the immune response also were found: Serum corticosterone levels were elevated on the eighth day of the response, and PO/AH tissue levels of norepinephrine were reduced between the sixth and tenth days. During induction of a secondary response, PO/AH MUA showed a different profile of activity from that recorded during the first response. Chronic administration of the immunosuppressive drug, cyclophosphamide, prevented the recorded changes in PO/AH MUA. These results suggest that some secretory product(s) of the activated immune system may be able to exert effects on the central nervous system. Various immunoactive substances therefore were administered intra-cerebroventricularly in order to examine their effects upon PO/AH MUA, cortical EEG and adrenocortical hormone secretory activity. alpha-Interferon and thymic humoral factor were both found to decrease PO/AH MUA, increase EEG synchronization, and decrease basal levels of circulating corticosterone. In contrast, histamine and interleukin-1 did not alter PO/AH MUA but did cause decreased EEG synchronization and increased serum corticosterone levels. With another preparation, a specific activating effect of interleukin-1 upon putative corticotropin-releasing factor-secreting neurones has also been found, identified vasopressinergic neurones not being affected.
本文所展示的研究表明，免疫系统的活性能够对中枢神经系统产生显著影响。电生理记录显示，在用绵羊红细胞致敏后，视前区/下丘脑前部（PO/AH）的多单位电活动（MUA）发生了显著变化。免疫后第五天出现活动峰值，这也是首次检测到血清抗体的同一天。室旁核MUA也出现了显著增加，但相对于PO/AH中的增加似乎有所延迟，在第六天出现。还发现了其他一些被认为与免疫反应相关的变化：反应第八天血清皮质酮水平升高，第六至十天PO/AH组织中的去甲肾上腺素水平降低。在二次反应诱导期间，PO/AH MUA的活动模式与首次反应期间记录的不同。长期给予免疫抑制药物环磷酰胺可阻止PO/AH MUA中记录到的变化。这些结果表明，活化免疫系统的某些分泌产物可能能够对中枢神经系统产生影响。因此，将各种免疫活性物质脑室内给药，以检查它们对PO/AH MUA、皮质脑电图和肾上腺皮质激素分泌活动的影响。发现α-干扰素和胸腺体液因子均可降低PO/AH MUA、增加脑电图同步性，并降低循环皮质酮的基础水平。相比之下，组胺和白细胞介素-1并未改变PO/AH MUA，但确实导致脑电图同步性降低和血清皮质酮水平升高。在另一项实验中，还发现白细胞介素-1对假定的促肾上腺皮质激素释放因子分泌神经元具有特异性激活作用，而确定的血管加压素能神经元未受影响。
