Reiche Edna Maria Vissoci, Morimoto Helena Kaminami, Nunes Sandra Morimoto Vargas
Department of Pathology, Clinical Analysis and Toxicology, State University of Londrina, Londrina, Paraná, Brazil.
Int Rev Psychiatry. 2005 Dec;17(6):515-27. doi: 10.1080/02646830500382102.
The persistent activation of the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary axes in chronic stress response and in depression impairs the immune response and contributes to the development and progression of some types of cancer. This overview presents results from experimental animal models, human studies, and clinical evidence that various cellular and molecular immunological parameters are compromised in chronic stress and depression. At the cellular level, stressed and depressed patients had overall leukocytosis, high concentrations of circulating neutrophils, reduced mitogen-stimulated lymphocyte proliferation and neutrophil phagocytosis. At the molecular level, high levels of serum basal cortisol, acute phase proteins, specific antibodies against herpes simplex virus type 1 and Epstein Barr virus, plasma concentration of interleukins IL-1, IL-6, and TNF-alpha, and a shift in the balance of Th1 and Th2 immune response were observed. Both stress and depression were associated with the decreased cytotoxic T-cell and natural killer cell activities affecting the processes of the immune surveillance of tumours, and the events that modulate the development and the accumulation of somatic mutations and genomic instability. DNA damage, growth and angiogenic factors, proteases, matrix metalloproteinases, and reactive oxygen species were also related to the chronic stress response and depression. Behavioural strategies, psychological, and psychopharmacotherapeutic interventions that enhance effective coping and reduce affective distress showed beneficial effects in cancer patients. A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to novel clinical and treatment strategies in oncology.
在慢性应激反应和抑郁症中，下丘脑 - 垂体 - 肾上腺轴以及交感 - 肾上腺 - 髓质轴的持续激活会损害免疫反应，并促进某些类型癌症的发生和发展。本综述展示了来自实验动物模型、人体研究以及临床证据的结果，表明在慢性应激和抑郁症中，各种细胞和分子免疫学参数均受到损害。在细胞水平上，处于应激和抑郁状态的患者总体上存在白细胞增多、循环中性粒细胞浓度升高、丝裂原刺激的淋巴细胞增殖减少以及中性粒细胞吞噬作用降低的情况。在分子水平上，观察到血清基础皮质醇、急性期蛋白、抗1型单纯疱疹病毒和EB病毒的特异性抗体、白细胞介素IL - 1、IL - 6和肿瘤坏死因子 - α的血浆浓度升高，以及Th1和Th2免疫反应平衡发生转变。应激和抑郁症均与细胞毒性T细胞和自然杀伤细胞活性降低有关，这会影响肿瘤免疫监视过程，以及调节体细胞突变和基因组不稳定的发生与积累的事件。DNA损伤、生长和血管生成因子、蛋白酶、基质金属蛋白酶以及活性氧也与慢性应激反应和抑郁症有关。行为策略、心理和心理药物治疗干预措施，若能增强有效应对能力并减轻情感困扰，则对癌症患者显示出有益效果。更好地理解神经内分泌系统与免疫系统之间的双向通信，可能有助于肿瘤学领域的新型临床和治疗策略的发展。
