Grinevich Valery, Harbuz Michael, Ma Xin-Ming, Jessop David, Tilders Fred J H, Lightman Stafford L, Aguilera Greti
Section on Endocrine Physiology, National Institute of Child Health and Human Development/NIH, Building 10, Room 10N262, 10 Center Drive, Bethesda, MD 20892-1862, USA.
Exp Neurol. 2002 Nov;178(1):112-23. doi: 10.1006/exnr.2002.8022.
We investigated the effect of immune challenge with LPS in both control rats and rats with adjuvant-induced arthritis (AA). Fourteen day-AA rats showed the expected activation of the hypothalamic-pituitary adrenal axis associated with increases in vasopressin mRNA and paradoxical decreases in corticotropin-releasing hormone (CRH) mRNA in parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). However, following LPS there was an increase in both CRH and vasopressin mRNA in the PVN. Neither control rats nor rats with AA had measurable plasma levels of IL-6, but plasma levels of IL-1beta were 2.7-fold higher in AA animals. Following LPS injection both IL-1beta and IL-6 increased more markedly in AA than in control rats. Neither controls nor AA rats expressed IL-1beta or IL-6 mRNA in the brain. However, following LPS these were induced in the subfornical organ, choroid plexus, and median eminence of both groups of animals. The areas expressing IL-1b mRNA were larger in the AA animals and exhibited a punctate pattern throughout the brain parenchyma and PVN. These data reveal an increased peripheral and central immunological response to LPS during the chronic inflammatory process of AA, providing a mechanism through which inflammatory disease can influence the response to a novel immunological challenge.
我们研究了脂多糖（LPS）免疫刺激对对照组大鼠和佐剂诱导性关节炎（AA）大鼠的影响。患AA 14天的大鼠表现出预期的下丘脑-垂体-肾上腺轴激活，伴有室旁核（PVN）小细胞神经元中血管加压素mRNA增加以及促肾上腺皮质激素释放激素（CRH）mRNA反常减少。然而，给予LPS后，PVN中CRH和血管加压素mRNA均增加。对照组大鼠和患AA大鼠的血浆IL-6水平均不可测，但AA动物的血浆IL-1β水平高2.7倍。注射LPS后，AA大鼠的IL-1β和IL-6增加比对照组大鼠更明显。对照组大鼠和患AA大鼠的大脑均不表达IL-1β或IL-6 mRNA。然而，给予LPS后，两组动物的穹窿下器官、脉络丛和正中隆起均诱导表达这些因子。表达IL-1β mRNA的区域在AA动物中更大，且在整个脑实质和PVN中呈点状分布。这些数据揭示了在AA慢性炎症过程中对LPS的外周和中枢免疫反应增强，为炎症性疾病影响对新的免疫刺激的反应提供了一种机制。
