Wiest Reiner, Moleda Lukas, Zietz Bettina, Hellerbrand Claus, Schölmerich Jürgen, Straub Rainer
Department of Internal Medicine, Regensburg University Medical Center, Regensburg, Germany.
J Gastroenterol Hepatol. 2008 Dec;23(12):1901-8. doi: 10.1111/j.1440-1746.2008.05456.x. Epub 2008 Jun 12.
The hypothalamic-autonomic nervous system (HANS) axis and the hypothalamic-pituitary-adrenal (HPA) axis are stimulated in parallel in response to stress factors under healthy conditions. This physiological synergism of the axes aims at optimizing anti-inflammatory actions. Therefore, we investigated whether this synergism is altered in patients with liver cirrhosis.
As a typical marker of the HANS axis neuropeptide Y (NPY is a neurotransmitter of the sympathetic nerve terminal) and of the HPA axis, cortisol together with adrenocorticotropic hormone (ACTH) and cortisol-binding globulin (CBG), were measured in samples from control subjects and patients with liver cirrhosis.
Plasma NPY was found to be increased in cirrhotic patients compared to control subjects (P < 0.01). This increase was observed to be independent of the severity of liver disease (Child class). Serum cortisol was decreased in cirrhotics, particularly in patients with Child A cirrhosis. Plasma NPY was positively correlated with serum cortisol in control subjects (r = 0.32, P < 0.05) reflecting the parallel activation of both axes under the normal condition. However, serum cortisol was not correlated with plasma NPY in cirrhotic patients. For the subgroup of Child A patients, even a negative correlation between NPY and cortisol was observed (r = -0.43, P < 0.05). No significant change in serum levels of ACTH and its positive correlation with serum cortisol was observed in cirrhotic patients.
The present study demonstrates that the two stress axes seem to act in parallel fashion in control subjects but are uncoupled in liver cirrhosis. We discuss how uncoupling of the two anti-inflammatory axes can occur and may contribute to the increased susceptibility for infections and lethal complications in cirrhotic patients.
在健康状态下，下丘脑 - 自主神经系统（HANS）轴和下丘脑 - 垂体 - 肾上腺（HPA）轴会因应激因素而同时受到刺激。这两个轴的这种生理协同作用旨在优化抗炎作用。因此，我们研究了肝硬化患者中这种协同作用是否发生改变。
作为HANS轴神经肽Y（NPY是交感神经末梢的神经递质）以及HPA轴的典型标志物，在来自对照受试者和肝硬化患者的样本中测量了皮质醇、促肾上腺皮质激素（ACTH）和皮质醇结合球蛋白（CBG）。
与对照受试者相比，肝硬化患者血浆NPY升高（P < 0.01）。观察到这种升高与肝病严重程度（Child分级）无关。肝硬化患者血清皮质醇降低，尤其是Child A级肝硬化患者。在对照受试者中，血浆NPY与血清皮质醇呈正相关（r = 0.32，P < 0.05），反映了正常情况下两个轴的平行激活。然而，肝硬化患者血清皮质醇与血浆NPY无相关性。对于Child A级患者亚组，甚至观察到NPY与皮质醇呈负相关（r = -0.43，P < 0.05）。肝硬化患者血清ACTH水平无显著变化，且其与血清皮质醇无正相关。
本研究表明，在对照受试者中两个应激轴似乎以平行方式起作用，但在肝硬化中则解偶联。我们讨论了两个抗炎轴解偶联如何发生以及可能如何导致肝硬化患者感染易感性增加和致命并发症。
