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Capacity to Produce Cytokines During Weight Restoration in Patients With Anorexia Nervosa

From the Department of Neuropsychiatry, Osaka City University Medical School, Osaka, Japan.

Address reprint requests to: Toshihiko Nagata, MD, PhD, Department of Neuropsychiatry, Osaka City University Medical School, 1-4-3, Asahimachi, Abenoku, Osaka 545-8585, Japan. Email: toshi{at}med.osaka-cu.ac.jp

OBJECTIVE: Anorexic patients are surprisingly free of infectious complications despite their seriously undernourished state. To study this phenomenon, we longitudinally measured the capacity to produce cytokines in restricting-type anorexic patients.

METHODS: Lymphoproliferative responses with phytohemagglutinin (PHA) and the capacity of whole blood to produce cytokines, such as interleukin-1 (IL-1), IL-6, tumor necrosis factor- (TNF-), interferon- (IFN-), and granulocyte-colony stimulating factor (G-CSF), were longitudinally measured before and after weight gain, that is, at admission and at less than 60, 65, and 75% of standard body weight (SBW), in 17 patients with restricting-type anorexia nervosa and in 17 control subjects.

RESULTS: Cytokine production of IL-1, IL-6, and TNF- per monocyte in the anorexic patients recovered only with the start of refeeding, whereas IFN- production per lymphocyte was similar to that in control subjects and did not change during weight restoration. Only G-CSF production, even at 75% SBW, did not improve during weight restoration. Between the weight at admission and 65% SBW, the increase in the percentage of SBW and improvement of the total protein level were significantly correlated with improvement of the lymphocyte proliferative response with PHA.

CONCLUSIONS: The capacity to produce most cytokines recovered with the start of weight gain; however, recovery was not correlated with weight gain. The results suggest that the capacity to produce cytokines in these anorexic patients was dependent on something other than the absolute value of body weight, such as the start of refeeding, the neuroendocrine system, or the autonomic nervous system.

Key Words: anorexia nervosa • cytokine • lymphocyte • monocyte • nutrition

Abbreviations: HPA axis = hypothalamo-pituitary-adrenal axis; LPS =lipopolysaccharide; IL = interleukin; TNF- = tumor necrosisfactor-; PHA = phytohemagglutinin; G-CSF =granulocyte-colony stimulating factor; IFN- = interferon-; SBW = standard body weight; PBMC = peripheral bloodmononuclear cell; ELISA = enzyme-linked immunosorbent assay; ANOVA = analysis of variance; TGF-ß = transforming growthfactor-ß; DST = dexamethasone suppression test.

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