Kamath Jayesh
Department of Psychiatry, The Carol and Ray Neag Comprehensive Cancer Center University of Connecticut Health Center, USA.
Curr Aging Sci. 2012 Dec;5(3):195-202. doi: 10.2174/1874609811205030005.
Aging and aging related illnesses such as cancer have been associated with inflammatory changes. Cancer-related behavioral comorbidities such as fatigue, sleep disturbances, depression have also been associated with inflammation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and other neuroendocrine changes. From a clinical perspective, cancer-related fatigue demonstrates striking similarities with the cytokine-induced sickness phenomenon in animal models. Thyrotopin-releasing hormone (TRH) plays a homeostatic role in its interaction with several biological systems, including a critical role in its interactions with the immune system. Considerable evidence supports a pivotal role for TRH in the inflammatory processes with specific relevance to the "cytokine-induced sickness behavior" paradigm. Additionally, TRH exerts arousing and analeptic effects in instances of behavioral depression. In a small proof-of-concept study conducted by our group, we investigated TRH administration as a treatment fatigue in cancer survivors in comparison with saline administration using a double-blind, crossover design. We also evaluated impact of TRH/saline administration on the inflammatory markers in these patients. TRH administration was associated with significant improvement (p < 0.05) in fatigue levels as measured by the Visual Analog Scale-Energy (VAS-E), was associated with significant (p < 0.05) improvement in sleep disturbances and improved quality of life. Notably, TRH administration was associated with decrease in C-reactive protein (CRP) levels, a marker of inflammation. This decrease in CRP level with TRH administration was associated with improvement in energy levels as measured by the VAS-E. The present review supports potential utility of TRH-based therapeutics in medical and psychiatric disorders with underlying inflammatory processes.
衰老以及癌症等与衰老相关的疾病都与炎症变化有关。与癌症相关的行为共病，如疲劳、睡眠障碍、抑郁等，也与炎症、下丘脑-垂体-肾上腺（HPA）轴功能失调以及其他神经内分泌变化有关。从临床角度来看，癌症相关疲劳与动物模型中细胞因子诱导的疾病现象有显著相似之处。促甲状腺激素释放激素（TRH）在与多个生物系统的相互作用中发挥着稳态作用，包括在与免疫系统相互作用中的关键作用。大量证据支持TRH在炎症过程中起关键作用，尤其与“细胞因子诱导的疾病行为”范式相关。此外，TRH在行为抑郁的情况下具有兴奋和提神作用。在我们小组进行的一项小型概念验证研究中，我们采用双盲、交叉设计，研究了与注射生理盐水相比，注射TRH对癌症幸存者疲劳的治疗效果。我们还评估了注射TRH/生理盐水对这些患者炎症标志物的影响。通过视觉模拟量表-能量（VAS-E）测量，注射TRH与疲劳水平的显著改善（p < 0.05）相关，与睡眠障碍的显著（p < 0.05）改善和生活质量的提高相关。值得注意的是，注射TRH与炎症标志物C反应蛋白（CRP）水平的降低相关。注射TRH后CRP水平的降低与通过VAS-E测量的能量水平的改善相关。本综述支持基于TRH的疗法在具有潜在炎症过程的医学和精神疾病中的潜在效用。
