Hypothesis: Cytokines play important roles in the pathogenesis of eating disorders, including anorexia nervosa and bulimia nervosa, and in obesity, and/or the medical complications associated with these illnesses. The eating disorders are serious illnesses characterized by a variety of behavioral, endocrine, and immune abnormalities. In preliminary studies, levels of two cytokines, interleukin-6 (lL-6) and transforming growth factor-beta (TGF-beta) were significantly elevated in anorexia nervosa and normalized with treatment. Since cytokines act as mediators of communication between the brain and the immune and endocrine systems, we reasoned that changes in cytokine production might be critical in eating disordered patients. Altered cytokine production might be a primary etiologic defect in eating disorders; alternatively, changes in cytokine levels might be secondary to weight change and subsequently contribute to perpetuation of disordered eating and/or contribute to the associated abnormal endocrine or immune function. To determine the role of cytokines in eating disorders, we will study cytokine production in three groups of patients before, during and after treatment- anorectics in an intensive inpatient program, obese patients on a very-low-calorie diet and bulimics undergoing treatment. To distinguish between effects due to disordered eating per se versus non-specific effects of weight loss or gain, we will also study cytokine patterns in two control groups of non-eating disordered women: controls who initially weigh 120-130% of ideal body weight and are on a weight reduction diet and normal weight controls without dietary intervention. I- Determine abnormalities of cytokines in eating disordered patients and determine the effect of successful treatment on cytokine abnormalities: Cytokines known to modulate feeding behavior or to regulate the immune and endocrine systems will be studied, specifically TNF-alpha, IL-1, IL-2, IL- 4, IL-6, gamma-IFN and TGF-beta. Levels of cytokines in patients' serum will be measured to estimate in vivo levels. In addition, production of cytokines by immune cells in vitro will be measured as an assessment of local production of cytokines. II- Correlate abnormal cytokine levels with changes in the immune cells that 1) produce the cytokines and 2) are regulated by the cytokines: A major site of cytokine production is immune cells; in addition, these cytokines regulate immune cell numbers and function. Numbers and functions of immune cells, specifically lymphocytes and monocyte/macrophages, are altered in many eating disordered patients. Therefore, identified abnormal cytokine levels will be correlated with changes in the numbers and functions of monocytes/macrophages and lymphocytes. III- Correlate abnormal cytokine levels with major endocrine and immune parameters known to be abnormal in patients with eating disorders: Cytokines have a variety of regulatory effects on endocrine and immune functions. Further, eating disorders are characterized by abnormalities of the endocrine and immune systems. Therefore, identified abnormal cytokine levels will be correlated with a battery of endocrine and immune function tests. Taken together, these studies will provide important insights into the role of abnormal cytokines in the pathogenesis of eating disorders and/or the associated medical complications and the mechanisms of the bidirectional interactions between cytokine production and endocrine and immune system dysregulation in patients with eating disorders.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Psychobiological, Biological, and Neurosciences Subcommittee (MHAI)
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Yanovski, Susan Z
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University of Kentucky
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United States
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Frederich, Robert; Hu, Shousheng; Raymond, Nancy et al. (2002) Leptin in anorexia nervosa and bulimia nervosa: importance of assay technique and method of interpretation. J Lab Clin Med 139:72-9
Raymond, N C; Dysken, M; Bettin, K et al. (2000) Cytokine production in patients with anorexia nervosa, bulimia nervosa, and obesity. Int J Eat Disord 28:293-302
Eckert, E D; Pomeroy, C; Raymond, N et al. (1998) Leptin in anorexia nervosa. J Clin Endocrinol Metab 83:791-5