Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas.

Jones, T. Hugh; Daniels, Mark; James, Roberta; Justice, S.; McCorkle, Robert; Price, A.; Kendall‐Taylor, P.; Weetman, A. P.

doi:10.1210/jcem.78.1.8288702

Cited by 45 publications

(22 citation statements)

References 4 publications

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“…IL-6 may support adenoma development and pathophysiology by autocrine/paracrine mechanisms since it has been reported to be synthesised and released by about 53 to 72% of pituitary adenomas (19,29). We observed heterogeneous IL-6 secretion in eight out of 11 (73%) somatotroph adenoma cell cultures in vitro, which is in agreement with previous findings.…”

Section: Discussionsupporting

confidence: 92%

Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

et al. 2003

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Objective: Interleukin-6 (IL-6), a member of the gp130 cytokine family, is considered to be an important modulator of function and growth in endocrine anterior pituitary cells. In pituitary adenomas, where IL-6 is often produced by the tumour cells, it is thought to be involved in pituitary adenoma pathophysiology via autocrine/paracrine mechanisms. Methods: We have studied in primary cell cultures of human somatotroph adenomas whether IL-6 stimulates growth hormone secretion and whether intratumoral IL-6 is affected by various IL-6-regulating factors.Results: Interleukin-6 stimulated GH secretion in 10 out of 11 somatotroph adenoma cultures (1.4-to 6.5-fold above basal levels). In comparative studies the GH-stimulatory potency of IL-6 was identical, or even stronger, than that of GHRH. In eight out of 11 adenoma cell cultures, IL-6 production was observed. This suggests that GH production might be stimulated by IL-6 in an autocrine/paracrine manner in these tumours. Dexamethasone strongly inhibited basal IL-6 secretion in all IL-6-producing adenoma cell cultures, whereas the IL-6 inhibitory or stimulatory action of other factors (octreotide, transforming growth factor-b1, insulin-like growth factor-I, pituitary adenylate cyclase-activating peptide and oestradiol) were heterogeneous in the different adenomas. Only transforming growth factor-a consistently stimulated IL-6 secretion in all of the adenomas studied. Conclusions: Intratumoral IL-6, which is differently regulated by various factors, might contribute to excessive GH production in the majority of somatotroph adenomas.

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Section: Discussionsupporting

confidence: 92%

Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

et al. 2003

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“…First demonstrated by Jones et al, secretion of IL6 by these tumours was seen to be independent of subtype (6), as confirmed by IL6 mRNA detection (7,8). The production in the normal gland is believed to be by FS cells (9); however, in pituitary adenomas, it is the tumour cells which are the source of production (10).…”

Section: Introductionmentioning

confidence: 72%

Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells

Borg

Kerry²,

Royds³

et al. 2005

eur j endocrinol

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Objectives: Vascular endothelial growth factor (VEGF) is considered to be the most important angiogenic factor involved in the neovascularisation of solid tumours. Regulatory molecules include cytokines and growth factors. Interleukin (IL)1 and IL6 have both been shown to regulate VEGF levels in a variety of tissues. The role of cytokines in the pathogenesis of pituitary tumours remains unclear. We have examined the expression of VEGF and its relationships with IL1 and IL6 in the human pituitary tumour cell line HP75 and a series of human pituitary tumours. We have also looked at the relationship of tumour volume and invasive status to VEGF secretion. Methods: Surgically resected tumours were routinely cultured in single-cell suspension at 200 K/well (standard unit for culture of dispersed primary pituitary adenoma cells). We measured VEGF, IL1a and IL6 levels by ELISA. Tumour volume and invasion grade were assessed by preoperative magnetic resonance imaging. Results: VEGF was detected in conditioned medium of HP75 cells (900^52 pg/ml) and in 82% of tumours tested (range 26-16 464 pg/ml). Tumour volume and secretion of VEGF were significantly associated with levels of IL6 (volume, P ¼ 0.056; VEGF, P , 0.001 (P values based on Spearman's test)) and IL1a produced (volume, P , 0.005; VEGF, P , 0.001). Invasive tumours showed a higher basal secretion of VEGF that that of the non-invasive type; however, this difference was not significant. Addition of exogenous IL1a, but not IL6, significantly increased VEGF production. Conclusions: The significant associations between VEGF and the levels of IL6 and IL1a suggest an important role for these cytokines in the development of these tumours.European Journal of Endocrinology 152 293-300

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“…The technique of RT-PCR, however, does not define the cells of origin, particularly whether or not the source is the neoplastic cell or other nonadenomatous cells such as fibroblasts, macrophages or endothelial cells. Immunoreactive and bioreactive IL-6 is known to be secreted by between 50 and 60% of pituitary adenomas, independent of the tumour type (6). Moreover, the IL-6 mRNA has been demonstrated, by in situ hybridisation, to be present in the adenomatous cells of the pituitary tumours (6).…”

Section: Introductionmentioning

confidence: 99%

“…Immunoreactive and bioreactive IL-6 is known to be secreted by between 50 and 60% of pituitary adenomas, independent of the tumour type (6). Moreover, the IL-6 mRNA has been demonstrated, by in situ hybridisation, to be present in the adenomatous cells of the pituitary tumours (6).…”

Section: Introductionmentioning

confidence: 99%

IL-8 mRNA expression by in situ hybridisation in human pituitary adenomas

Suliman

Royds²,

Baxter³

et al. 1999

European Journal of Endocrinology

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Several cytokines have been shown to be expressed in normal and adenomatous pituitary tissue. Recently, interleukin-8 (IL-8) mRNA was identified by reverse transcription (RT)-PCR in each of a series of 17 pituitary tumours examined. We have investigated further the presence of IL-8 mRNA, using in situ hybridisation in two normal human anterior pituitary specimens and 25 human pituitary adenomas. IL-8 mRNA was not identified in either of the two normal pituitary specimens. Only three of the 25 adenomas were positive for IL-8 mRNA. In these three tumours, which included two null cell adenomas and one gonadotrophinoma, the majority of tumour cells (>90%) were positive for IL-8 mRNA. The remaining 22 adenomas were completely negative. There was no difference in tumour size or type between the IL-8 positive and the IL-8 negative tumours, and immunocytochemistry for von Willebrandt factor showed that the two groups were also similar in their degree of vascularisation.In conclusion, IL-8 mRNA was found in 12% of pituitary adenomas studied and was histologically identified within the tumour cells. In situ hybridisation is a more appropriate technique for assessing cytokine mRNA production by human pituitary tumours because RT-PCR may be too sensitive, identifying very small, possibly pathologically insignificant, quantities of mRNA that could be produced by supporting cells such as fibroblasts, endothelial cells or macrophages. European Journal of Endocrinology 140 155-158

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Production of bioactive and immunoreactive interleukin-6 (IL-6) and expression of IL-6 messenger ribonucleic acid by human pituitary adenomas.

Cited by 45 publications

References 4 publications

Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

Functional in vitro studies on the role and regulation of interleukin-6 in human somatotroph pituitary adenomas

Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells

IL-8 mRNA expression by in situ hybridisation in human pituitary adenomas

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