Holden R J, Pakula I S
Medical Research Unit, University of Wollongong, NSW, Australia.
Med Hypotheses. 1996 Dec;47(6):423-38. doi: 10.1016/s0306-9877(96)90153-x.
In this paper a new immunological model of anorexia and bulimia nervosa will be presented in which the inflammatory cytokines are conceived as the fundamental regulators of body metabolism. This conception differs from the conventional view in which the inflammatory cytokines are perceived primarily as peptide molecules utilized by the immune system to control infection, inflammation and tissue or neuronal damage. Given that the inflammatory cytokines are also fundamental regulators of body metabolism, when they become dysregulated they create physiological chaos which results in the development of a number of autoimmune, metabolic and psychiatric disorders. In this proposed immunological model of anorexia and bulimia nervosa, elevated tumor necrosis factor-alpha features as the primary cause of these conditions. Pathophysiological parallels are drawn between anorexia nervosa and cancer cachexia in terms of the causal role the cytokines, neuropeptides and neurotransmitters play in the manifestation of shared symptoms. These shared symptoms include elevated tumour necrosis factor-alpha, down-regulated interleukin-2 and interleukin-4 and depletion of lean body mass. Furthermore, the following neuropeptides are dysregulated in both anorexia nervosa and cancer cachexia: vasoactive intestinal peptide, cholecystokinin, corticotropin-releasing factor, neuropeptide Y, peptide YY and beta-endorphin. In addition, in anorexia and bulimia nervosa, secretion of the neurotransmitter serotonin is inhibited while norepinephrine is enhanced. It will be argued that the causal interplay between the cytokines, neuropeptides and neurotransmitters initiates a cascade of biochemical events which may result in either anorexia or bulimia nervosa, or cancer cachexia. The extent to which these inflammatory cytokines, neuropeptides and neurotransmitters are causally efficacious in the pathogenesis of other autoimmune disorders, such as diabetes mellitus and rheumatoid arthritis, will also be addressed.
本文将提出一种神经性厌食症和神经性贪食症的新免疫模型，其中炎性细胞因子被视为身体新陈代谢的基本调节因子。这一概念与传统观点不同，传统观点认为炎性细胞因子主要是免疫系统用来控制感染、炎症以及组织或神经元损伤的肽分子。鉴于炎性细胞因子也是身体新陈代谢的基本调节因子，当它们失调时就会引发生理紊乱，从而导致多种自身免疫性、代谢性和精神性疾病的发生。在这个提出的神经性厌食症和神经性贪食症免疫模型中，肿瘤坏死因子-α升高是这些病症的主要原因。从细胞因子、神经肽和神经递质在共同症状表现中所起的因果作用方面，对神经性厌食症和癌症恶病质的病理生理相似性进行了探讨。这些共同症状包括肿瘤坏死因子-α升高、白细胞介素-2和白细胞介素-4下调以及瘦体重减少。此外，在神经性厌食症和癌症恶病质中，以下神经肽均失调：血管活性肠肽、胆囊收缩素、促肾上腺皮质激素释放因子、神经肽Y、肽YY和β-内啡肽。另外，在神经性厌食症和神经性贪食症中，神经递质血清素的分泌受到抑制，而去甲肾上腺素分泌增强。有人认为，细胞因子、神经肽和神经递质之间的因果相互作用引发了一系列生化事件，这可能导致神经性厌食症或神经性贪食症，或癌症恶病质。这些炎性细胞因子、神经肽和神经递质在其他自身免疫性疾病（如糖尿病和类风湿性关节炎）发病机制中的因果效力程度也将得到探讨。
