The role of tumor necrosis factor-alpha in the pathogenesis of anorexia and bulimia nervosa, cancer cachexia and obesity.
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.
Holden
R J
RJ
Medical Research Unit, University of Wollongong, NSW, Australia.
Pakula
I S
IS
D000856:Anorexia Nervosa / Q000209:etiology* / Q000276:immunology; D002032:Bulimia / Q000209:etiology* / Q000276:immunology; D002100:Cachexia / Q000209:etiology* / Q000276:immunology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008954:Models, Biological; D009479:Neuropeptides / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D009765:Obesity / Q000209:etiology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D016207:Cytokines; D018836:Inflammation Mediators; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D014409:Tumor Necrosis Factor-alpha