Harbour D V, Smith E M, Blalock J E
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Brain Behav Immun. 1987 Jun;1(2):123-33. doi: 10.1016/0889-1591(87)90015-8.
Endogenous opioids have been reported to elicit some of the pathophysiologic responses to endotoxic shock by binding to the delta-opiate receptor. We have previously reported the production of immunoreactive (ir)-endorphin by B lymphocytes treated with bacterial lipopolysaccharide (LPS). We postulated that this lymphocyte-derived ir-endorphin may be an extrapituitary source of the endogenous opioid component associated with the pathophysiology of endotoxic shock. To test this hypothesis, we chose to study the LPS-sensitive (C3HeB/FeJ) and -resistant (C3H/HeJ) inbred mouse model. We treated these mice with intraperitoneal injections of LPS or B-lymphocyte-derived ir-endorphin. The LPS-sensitive mice presented with a severe hypothermic and pathophysiologic response pattern when treated with LPS or with ir-endorphin. The LPS-resistant mice, which were unresponsive to the LPS, however, presented with the typical hypothermic and pathophysiologic responses to the ir-endorphin. Immunofluorescence on the splenic leukocytes in the LPS-treated mice showed significant ir-endorphin present only in the LPS-sensitive mice at a time point preceding onset of the pathophysiologic response pattern. Taken together, this evidence strongly suggests a role for B-lymphocyte-derived ir-endorphin in the pathophysiology of endotoxic shock. The implications of immune system regulation of neuroendocrine function are discussed.
据报道，内源性阿片类物质通过与δ-阿片受体结合引发对内毒素休克的一些病理生理反应。我们之前曾报道，经细菌脂多糖（LPS）处理的B淋巴细胞可产生免疫反应性（ir）-内啡肽。我们推测，这种淋巴细胞源性ir-内啡肽可能是与内毒素休克病理生理学相关的内源性阿片类物质的垂体外来源。为了验证这一假设，我们选择研究LPS敏感（C3HeB/FeJ）和抗性（C3H/HeJ）近交小鼠模型。我们给这些小鼠腹腔注射LPS或B淋巴细胞源性ir-内啡肽。LPS敏感小鼠在接受LPS或ir-内啡肽治疗时呈现出严重的体温过低和病理生理反应模式。然而，对LPS无反应的LPS抗性小鼠对ir-内啡肽呈现出典型的体温过低和病理生理反应。对LPS处理小鼠脾白细胞的免疫荧光显示，在病理生理反应模式开始前的一个时间点，仅在LPS敏感小鼠中存在大量ir-内啡肽。综上所述，这些证据有力地表明B淋巴细胞源性ir-内啡肽在内毒素休克病理生理学中发挥作用。本文还讨论了免疫系统对神经内分泌功能调节的意义。
