Functional interleukin-6 receptor-α is located to tanycytes at the base of the third ventricle

Abstract

Interleukin-6 (IL-6) ^-/^- mice develop mature onset obesity, while intracerebroventricular (ICV) injection of IL-6 decreases obesity in rodents. Moreover, levels of IL-6 in cerebrospinal fluid (CSF) have been reported to be inversely correlated with obesity in humans. Tanycytes lining the base of the 3^rd ventricle in the hypothalamus have recently been reported to be of importance for metabolism. In the present study, we investigated whether tanycytes could respond to IL-6 in the CSF.

With immunohistochemistry using a well characterized antibody directed against the ligand binding receptor for IL-6, IL-6 receptor α (IL-6Rα), it was found that tanycytes, identified by the two markers vimentin and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), contained IL-6Rα. There were fewer IL-6Rα on another type of ventricle-lining cells, ependymal cells, identified by the marker glucose transporter-1 (GLUT-1).

To ascertain that the immunoreactive IL-6Rα were responsive to IL-6, we injected IL-6 ICV. This treatment increased immunoreactive phosphorylated STAT-3 (pSTAT-3) in tanycytes after 5 min and in cells in the medial part of the arcuate nucleus (ARC) after 5 and 15 min. ICV injection of leptin exerted similar effects. As expected, intraperitoneal (i.p.) injection of leptin also induced pSTAT-3 staining in the hypothalamus, while IP IL-6 injection had little effect on this parameter. ICV or IP injection of vehicle only had no effect on pSTAT3-immunoreactivity.

In summary, there are functional IL-6Rα on tanycytes at the bottom of the third ventricle (3V), in line with the possibility that ventricular administration of IL-6 decreases obesity in mice via an effect on this cell type.

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