Involvement of cytokines in eating disorders: a critical review of the human literature.

A number of findings from clinical and animal studies indicate that pro-inflammatory cytokines may play roles in eating disorders. The measurement of pro-inflammatory cytokines (IL-1, IL-6, TNFalpha), which are known to decrease food intake, provides highly variable data from which firm conclusions cannot be drawn. In most of the longitudinal studies where pro-inflammatory cytokines have been shown to be impaired in anorexia or bulimia nervosa, a return to normal values was observed after renutrition. However these findings do not exclude the possibility that pro-inflammatory cytokines might be overproduced in specific brain areas and act locally without concomitantly increased serum or immune production. It was also pointed out that the production of the major type-1 cytokines (especially IL-2) was depressed in anorexia nervosa. It remains unclear whether this is due to undernutrition or to a specific underlying cause common to eating disorders. The impaired cytokine profile observed in eating disorders could be related to several factors including impaired nutrition, psychopathological and neuroendocrine factors. More particular attention should be devoted to the deregulation of the anti/pro-inflammatory balance. Deregulation of the cytokine network may be responsible for medical complications in eating disorder patients who are afflicted with chronic underweight.

Increased cerebrospinal fluid 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in Kleine-Levin syndrome.

A 17-year-old man with the Kleine-Levin syndrome died unexpectedly of cardiopulmonary arrest during a period of autonomic instability that followed an episode of megaphagia. At autopsy, the only pertinent finding was mild depigmentation of the locus ceruleus and substantia nigra. Premortem CSF levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were elevated. These findings indicate that many symptoms of the Kleine-Levin syndrome are a result of a neurotransmitter imbalance in the serotonergic pathway of the brainstem.

Abnormal central monoamine metabolism in humans with "true hypersomnia" and "sub-wakefulness".

A case of Kleine-Levin syndrome with true hypersomnia and a case of sub-wakefulness are described. In both patients lumbar cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylethylene glycol levels have been assayed during episodes of hypersomnia and normal sleep-waking cycles. Besides an increased 5-hydroxytryptamine turnover, mainly an increased dopamine turnover has been detected in both kinds of hypersomnia, and this finding was more remarkable in the case with sub-wakefulness. The probable role of dopamine in abnormalities in the sleep-waking cycle is discussed on the basis of results in experimental animal hypersomnias.