Interleukin-6 and Mood Disorders in Endocrine Disease

There is mounting evidence that circulating cytokines play a crucial role in neuroendocrine system function. Furthermore, there appears to be a reciprocal relationship between the metabolic syndrome and mood disorders including depression. A recently published study provides further evidence for this important concept [1]. Identifying Interleukin-6 as a major factor linking inflammation, metabolic disease and depression, it has become clear that they form a cluster of diseases with overlapping pathomechanisms. However, this study reveals even broader clinical implications that should be examined in future studies. The significant correlation between IL-6 levels and mood ratings as well as IL-6’s possible involvement in depressive symptoms, regardless of cortisol levels, is of great interest to other endocrine disorders frequently associated with mood disturbances. For instance, thyroid disorders such as autoimmune thyroiditis have been associated with elevated levels of pro-inflammatory cytokines such as TNF-α and IL-6 [2]. Particularly, high circulating IL-6 levels have been reported in Graves’ ophthalmopathy, suggesting that the IL-6 cytokine may be an important factor in the inflammatory events associated with Graves’ ophthalmopathy [3].

Patients with moderate to severe Graves’ ophthalmopathy are known to have significant mood disturbances; the psychological burden of the disease should be considered in the treatment of these patients [4]. Therefore, it would be of interest to correlate IL-6 levels to the degree of emotional distress in this group of patients. Another common endocrine disease that has more recently been recognized to cause major depression in up to 10 % of patients is primary hyperparathyroidism [5]. Parathyroidectomy reduces symptoms of major depression in these patients. Interestingly, parathyroid tumors produce and secrete IL-6, and may contribute to the elevation of serum IL-6 levels in patients with hyperparathyroidism [6]. Thus, elevated IL-6 serum levels normalize after resection of parathyroid tumors. Finally, altered cytokine profiles, including those of IL-6, are observed in anorexia nervosa, an eating disorder with severe weight loss, emotional distress and multiple endocrine perturbations [7].

Although IL-6 is unlikely to be the only mediator affecting mood in these patients, these studies expand our view on IL-6 not only as an inflammatory cytokine but also as a hormonal factor that may be broadly connected to alterations in behavior and mood as seen in various endocrine disorders.

Abbreviations: IL-6, Interleukin-6

References

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