Habu S, Watanobe H, Yasujima M, Suda T
Third Department of Internal Medicine, Hirosaki University School of Medicine, Aomori, Japan.
Cytokine. 1998 May;10(5):390-4. doi: 10.1006/cyto.1997.0296.
Although it is well established that peripheral administration of endotoxin activates the hypothalamic-pituitary-adrenal (HPA) axis, information is very limited regarding whether central administration of endotoxin can similarly stimulate the endocrine axis. Moreover, it is also unknown whether a difference exists in the mode of involvement of brain-derived cytokines in determining the HPA response to peripheral vs central administration of endotoxin. In the present study, the authors attempted to gain more knowledge on these issues focusing on interleukin (IL) 1 in the brain, one of key pro-inflammatory cytokines mediating the immuno-endocrine network. In male rats, both intravenous (i.v., 100 micrograms/kg body weight) and intracerebroventricular [i.c.v. (the 3rd ventricle), 10 micrograms] injections of Escherichia coli lipopolysaccharide (LPS) caused a significant elevation of adrenocorticotropin (ACTH) levels in plasma, even though peaked ACTH responses occurred earlier after the i.v. (60 min post-injection) than the i.c.v. (120 min post-injection) LPS. Although the ACTH response to i.c.v. LPS was significantly suppressed by a prior (5 min) i.c.v. administration of IL-1 receptor antagonist (IL-1Ra, 1 microgram), the hormonal response to i.v. LPS was not. That this dose of IL-1Ra was not biologically a small dose was indicated by another experiment that the same dose of i.c.v. IL-1Ra was able to significantly suppress the ACTH response to an i.c.v. injection of recombinant human IL-1 beta (50 ng). These results suggest that i.c.v. LPS, as i.v. LPS, can stimulate ACTH secretion in the rat, and this hormonal response may, at least in part, be mediated by brain-derived IL-1. Although there is one previous study reporting an important role of central IL-1 in mediating the HPA response to systemic LPS treatment, our present data suggest that such a mechanism may not operate before and during an early, peak phase of ACTH secretion after i.v. LPS.
尽管外周给予内毒素可激活下丘脑 - 垂体 - 肾上腺（HPA）轴这一点已得到充分证实，但关于中枢给予内毒素是否能同样刺激该内分泌轴的信息却非常有限。此外，对于脑源性细胞因子在决定HPA对外周与中枢给予内毒素反应的参与模式上是否存在差异也尚不清楚。在本研究中，作者试图围绕脑中的白细胞介素（IL）-1（介导免疫 - 内分泌网络的关键促炎细胞因子之一）来获取有关这些问题的更多知识。在雄性大鼠中，静脉注射（i.v.，100微克/千克体重）和脑室内注射[i.c.v.（第三脑室），10微克]大肠杆菌脂多糖（LPS）均导致血浆中促肾上腺皮质激素（ACTH）水平显著升高，尽管静脉注射LPS后（注射后60分钟）ACTH反应峰值出现的时间早于脑室内注射LPS（注射后120分钟）。虽然在脑室内注射LPS前5分钟预先脑室内给予IL - 1受体拮抗剂（IL - 1Ra，1微克）可显著抑制ACTH反应，但对静脉注射LPS的激素反应却没有影响。另一项实验表明相同剂量的脑室内IL - 1Ra能够显著抑制对脑室内注射重组人IL - 1β（50纳克）的ACTH反应，这表明该剂量的IL - 1Ra在生物学上并非小剂量。这些结果表明，脑室内注射LPS与静脉注射LPS一样，可刺激大鼠ACTH分泌，且这种激素反应可能至少部分由脑源性IL - 1介导。尽管之前有一项研究报道中枢IL - 1在介导HPA对全身LPS治疗的反应中起重要作用，但我们目前的数据表明，在静脉注射LPS后ACTH分泌的早期峰值阶段之前及期间，这种机制可能并不起作用。
