Interleukin-6 and the Hypothalamic-Pituitary-Adrenal Activation in a Tumor Bearing Mouse

Lee, Jong-Ho; Yoo, Sang Bae; Kim, Nam Youl; Joo, Mi Kyoung; Jahng, Jeong Won

doi:10.1080/00207450701592915

Cited by 5 publications

(2 citation statements)

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“…Tumor derived cytokines have been suggested to activate the HPA axis [44,45]. Interestingly IL-6 in particular appears essential for activation of the HPA axis during immunological challenge in the absence of hypothalamic input from CRH [19].…”

Section: Resultsmentioning

confidence: 99%

Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism

et al. 2013

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BackgroundInterleukin (IL)-6 (mainly of tumor origin) activates glutathione (GSH) release from hepatocytes and its interorgan transport to B16-F10 melanoma metastatic foci. We studied if this capacity to overproduce IL-6 is regulated by cancer cell-independent mechanisms.MethodsMurine B16-F10 melanoma cells were cultured, transfected with red fluorescent protein, injected i.v. into syngenic C57BL/6J mice to generate lung and liver metastases, and isolated from metastatic foci using high-performance cell sorting. Stress hormones and IL-6 levels were measured by ELISA, and CRH expression in the brain by in situ hybridization. DNA binding activity of NF-κB, CREB, AP-1, and NF-IL-6 was measured using specific transcription factor assay kits. IL-6 expression was measured by RT-PCR, and silencing was achieved by transfection of anti-IL-6 small interfering RNA. GSH was determined by HPLC. Cell death analysis was distinguished using fluorescence microscopy, TUNEL labeling, and flow cytometry techniques. Statistical analyses were performed using Student’s t test.ResultsPlasma levels of stress-related hormones (adrenocorticotropin hormone, corticosterone, and noradrenaline) increased, following a circadian pattern and as compared to non-tumor controls, in mice bearing B16-F10 lung or liver metastases. Corticosterone and noradrenaline, at pathophysiological levels, increased expression and secretion of IL-6 in B16-F10 cells in vitro. Corticosterone- and noradrenaline-induced transcriptional up-regulation of IL-6 gene involves changes in the DNA binding activity of nuclear factor-κB, cAMP response element-binding protein, activator protein-1, and nuclear factor for IL-6. In vivo inoculation of B16-F10 cells transfected with anti-IL-6-siRNA, treatment with a glucocorticoid receptor blocker (RU-486) or with a β-adrenoceptor blocker (propranolol), increased hepatic GSH whereas decreased plasma IL-6 levels and metastatic growth. Corticosterone, but not NORA, also induced apoptotic cell death in metastatic cells with low GSH content.ConclusionsOur results describe an interorgan system where stress-related hormones, IL-6, and GSH coordinately regulate metastases growth.

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Section: Resultsmentioning

confidence: 99%

Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism

et al. 2013

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“…Other markers of chronic stress activation also include body weight fluctuations and changes in behavior, including depression and feeding behavior [10]. Interestingly, cancer, as a form of physiological stress, can also elicit these same responses [11].…”

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confidence: 99%

Alterations of Antitumor and Metabolic Responses in L5178y-R Lymphoma-Bearing Mice After Only 30-Minute Daily Chronic Stress Exposure

et al. 2017

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Aim: In stress research, reducing times of stress induction may contribute to improving the well-being of experimental animals, especially in cancer models, already under physiological distress. To support this idea, we evaluated the effects of a short-timed stress protocol on endocrine, metabolic and immune indicators in mice bearing the L5178Y-R lymphoma. Materials and Methods: A 30-minute daily stress protocol was applied for 28 days to healthy and lymphoma-bearing BALB/c mice; body weight, plasma levels of corticosterone, norepinephrine, Th1/Th2 cytokines, insulin, and leptin, were measured. Results: We found a 12% significant decrease in body weight in non-tumor bearing mice under stress (p < 0.007). The disruption of weight evolution was accompanied by a stress induced 85% decrease in plasmatic leptin (p < 0.01) and total reduction of insulin. Tumor burden alone was associated to an increase in more than two-fold of plasmatic levels of norepinephrine (p < 0.008). Neither stress nor tumor or their combination, resulted in an elevation of systemic IL-6. IFN-γ levels were 20 times higher in lymphoma-bearing animals when compared with non-tumor bearing mice (p < 0.01); however, under stress, this response was reduced by half, indicating a suppressing effect of chronic stress on the antitumor immune response. Conclusion: A short-timed stress induction is enough to cause significant alterations in the metabolism and immunity of healthy and tumor-bearing mice, supporting the use of short-timed protocols as an efficient way to induce chronic stress that also considers concerns regarding the well-being of experimental animals in biomedical research.

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Applications of Fungal Mycelium-Based Functional Biomaterials

Manan

Atta

Shahzad

et al. 2022

Fungal Biopolymers and Biocomposites

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Interleukin-6 and the Hypothalamic-Pituitary-Adrenal Activation in a Tumor Bearing Mouse

Cited by 5 publications

References 40 publications

Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism

Stress hormones promote growth of B16-F10 melanoma metastases: an interleukin 6- and glutathione-dependent mechanism

Alterations of Antitumor and Metabolic Responses in L5178y-R Lymphoma-Bearing Mice After Only 30-Minute Daily Chronic Stress Exposure

Applications of Fungal Mycelium-Based Functional Biomaterials

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