Interleukin-1α leads to growth hormone deficiency in adamantinomatous craniopharyngioma by targeting pericytes: implication in pituitary fibrosis

• Published in: Metabolism, clinical and experimental clinical and experimental, 2019-12, Vol.101, p.153998-153998, Article 153998
• Main Authors: Mao, Jian, Qiu, Binghui, Mei, Fen, Liu, Fan, Feng, Zhanpeng, Fan, Jun, Nie, Jing, Huang, Lijun, Liao, Xixian, Wang, Zhenhao, Zeng, Jiahui, Weng, Zelin, Zang, Nailiang, Qi, Songtao, Bao, Yun
• Format: Article
• Language: English
• Subjects: Adamantinomatous craniopharyngioma; Adult; Animals; Cell Communication; Craniopharyngioma - etiology; Craniopharyngioma - pathology; Cytokines - metabolism; Female; Fibrosis; Growth hormone deficiency; Human Growth Hormone - deficiency; Human Growth Hormone - drug effects; Human Growth Hormone - metabolism; Humans; Inflammation; Interleukin-1alpha - pharmacology; Interleukin-1α; Male; Pericytes; Pericytes - cytology; Pericytes - drug effects; Pituitary fibrosis; Pituitary Gland - metabolism; Pituitary Gland - pathology; Rats
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2019.153998

The incidence of growth hormone deficiency (GHD) in adamantinomatous craniopharyngioma (aCP) is significantly higher than in other sellar region tumors, but the possible mechanism is still elusive. A high level of inflammatory responses is another feature of aCP. We investigated the internal connection between interleukin-1α (IL-1α) and GHD, while focusing on its biological activities in pituitary fibrosis. To diagnosis of GHD, the Body Mass Index (BMI), Insulin Like Growth Factor-1(IGF-1) and peak growth hormone (GH) values after insulin stimulation test of 15 aCP patients were recorded. Histological staining was performed on the aCP samples. Levels of 9 proinflammatory cytokines in tumor tissue and cell supernatant were detected using Millipore bead arrays. The effect of IL-1α on GH secretion was evaluated in vivo and in vitro. Western blot, qRT-PCR and cell functional assays were used to explore the potential mechanism through which IL-1α acts on GH secretion. The stereotactic ALZET osmotic pump technique was used to simulate aCP secretion of proinflammatory cytokines in rats. Recombinant IL-1α (rrIL-1α) and conditioned media (CM) prepared from the supernatant of aCP cells was infused directly into the intra-sellar at a rate of 1 μl/h over 28 days, and then the effects of IL-1α treatment on pathological changes of pituitary gland and GH secretion were measured. To further confirm whether IL-1α affects GH secretion through IL-1R1, an IL-1R1 blocker (IL-1R1a, 10 mg/kg body weight, once daily) was administered subcutaneously from the first day until day 28. There was a significant positive correlation between pituitary fibrosis and GHD (rS = 0.756, P = 0.001). A number of cytokines, in particular IL-1α, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), were elevated in tumor tissue and cell supernatant. Only IL-1α showed a significant difference between the GHD group and the No-GHD group (P