Hormonal changes following tumor transplantation: Factors increasing corticosterone and the relationship of corticosterone to tumor‐induced anti‐inflammation

Normann, Sigurd J.; Besedovsky, Hugo O.; Schardt, M.; Rey, Adriana del

doi:10.1002/ijc.2910410613

Cited by 16 publications

(12 citation statements)

References 12 publications

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“…A number of these cytokines, including γ-interferon and tumour necrosis factor-α, may be secreted by tumours (Merz et al, 1991) and indeed the secretion of IL-6 has recently been shown to correlate with disease activity and to be associated with adverse prognostic features (Seymour et al, 1995). Furthermore, the experimental in vivo transplantation of lymphoma cells has been shown to markedly elevate glucocorticoid levels, an effect that can be mirrored by the transference of ascitic fluid from the lymphoma-bearing animal (Normann et al, 1988a(Normann et al, , 1988b. Whatever the precise mechanism underlying both the adrenal enlargement and disturbed pituitary-adrenal regulation, the question arises as to its functional significance.…”

Section: Discussionmentioning

confidence: 99%

Adrenal enlargement and failure of suppression of circulating cortisol by dexamethasone in patients with malignancy

et al. 1999

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The aim of this study was to further elucidate the activity of the hypothalamo–pituitary–adrenal (HPA) axis in patients with malignancy and to correlate this with the size of the adrenal glands. Fourteen patients with a variety of malignancies were studied prior to receiving cytotoxic chemotherapy. During routine staging computerized tomographic (CT) scans, the size of the body, medial and lateral limbs of the adrenal glands were measured and compared with those of a normal group of patients studied previously. Measurements of 09:00 h serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were made before and after the administration of dexamethasone (0.5 mg 6-hourly for 48 h) in addition to the peak cortisol response to i.v corticotropin releasing hormone (CRH). Overall, patients with malignancy had significantly larger adrenal glands than patients without malignancy; those with non-haematological malignancies had larger glands than patients with haematological malignancies. Following dexamethasone to suppress circulating cortisol levels, nine patients (64%) demonstrated abnormal resistance with cortisol levels > 50 nmol l −1 : mean value 294 nmol l −1 (range 67–1147). Those patients who failed to suppress after dexamethasone had significantly larger adrenal glands than those that did suppress and tended to have non-haematological malignancies. ACTH levels were undetectable or low in three patients in whom it was measured and who did not suppress with dexamethasone. Following CRH, the cortisol levels were highest (823 and 853 nmol l −1 ) in two of these patients. Malignancy is associated with diffuse enlargement of the adrenal glands and resistance to dexamethasone-induced suppression of the HPA axis, which is not due to ectopic ACTH secretion. This disturbance of the normal control of the HPA axis is unexplained and its functional significance remains uncertain. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 99%

Adrenal enlargement and failure of suppression of circulating cortisol by dexamethasone in patients with malignancy

et al. 1999

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“…It is known that endocrine balance is affected by tumor cell administration [47,48]. These endocrine imbalances occur very early and late after tumor transplantation [47].…”

Section: Discussionmentioning

confidence: 99%

Catecholamine, Indoleamine and Corticosteroid Responses in Mice Bearing Tumors

Chuluyan

Wolcott²,

Chervenak³

et al. 2000

Neuroimmunomodulation

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The neurochemical and endocrine responses to inoculation of mice with the murine lymphoma cell line AW5E was studied. This cell line was chosen because it is NK cell lysis resistant and thus does not induce a normal immune response. Immune activation has long been known to be a potent stimulator of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as brain catecholamine and indoleamine metabolism, involving increases in the brain concentrations of catabolites of norepinephrine (NE) and serotonin (5-HT), as well as free tryptophan. Mice injected intravenously with AW5E tumor cells exhibited small increases in plasma corticosterone and hypothalamic NE and 5-HT catabolites one day after injection. There were no significant changes after 6 or 8 days, but a sustained increase in hypothalamic NE and 5-HT metabolism appeared 10 days after injection. There were similar, but more limited changes in the brain stem and prefrontal cortex. On the last day tested (day 14), plasma corticosterone was slightly elevated, as were hypothalamic dopamine, NE and 5-HT catabolites and tryptophan. These results indicate that inoculation with AW5E tumor cells increases brain catecholamine and serotonin metabolism, the hypothalamus being the most sensitive region. The most marked increases occurred in the few days preceding death, and thus may be associated with the pathology of the tumor growth.

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“…It was previously clarified that serum corticosterone levels are increased in mice inoculated with EL-4, colon 26 tumor cells (31,44). These findings suggest that although glucocorticoid strongly suppressed Th1 responses, Th2 responses could be enhanced in tumor-bearing mice.…”

Section: Discussionmentioning

confidence: 99%

Anti‐Tumor Mechanism of Z‐100, an Immunomodulatory Arabinomannan Extracted from Mycobacterium tuberculosis Strain Aoyama B, on Pulmonary Metastases of B16F10 Melanoma: Restoration of Helper T Cell Responses via Suppression of Glucocorticoid‐Genesis

oka

Emori

Sasaki

et al. 2002

Microbiology and Immunology

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In the present study, the anti‐tumor mechanism of Z‐100 was investigated with the use of pulmonary metastasis of B16F10 melanoma. In B16F10 mice, Th1 cytokine production (IL‐2, IFN‐γ) was suppressed in comparison with normal mice. On the other hand, Th2 cytokine production (IL‐4, IL‐10) was increased in the B16F10 mice. The administration of Z‐100 to B16F10 mice restored the balance of Th1/Th2 cell responses from the Th2 dominant state to the normal state. Z‐100 significantly suppressed the pulmonary metastasis of B16F10 melanoma in a dose‐dependent manner. These results suggest that Z‐100 restored the breakdown of Th1 cell responses, resulting in the suppression of pulmonary metastasis of B16F10 melanoma. Moreover, Z‐100 decreased the corticosterone levels, which is known to suppress the Th1 cell responses, in both serum specimens and splenic tissue, and the steroidogenic CYP11A1 mRNA expression in CD4+ T cells. These results suggest that a suppression of pulmonary metastasis and restoration of Th1/Th2 cell responses by Z‐100 may be due to the decrease in the corticosterone levels and the steroidogenic CYP11A1 mRNA expression of CD4+ T cells in B16F10 mice. Further, the role of Th1 cytokine, IFN‐γ, on these activities of Z‐100 was examined. The suppressive effects of Z‐100 on pulmonary metastasis and restoration of Th1/Th2 cell responses were eliminated by the administration of anti‐IFN‐γ mAb. Moreover, the suppressive effects of Z‐100 on glucocorticoid‐genesis were eliminated by the administration of anti‐IFN‐γ mAb. These results suggest that Z‐100 restores the balance of Th1/Th2 cell responses via the suppression of glucocorticoid‐genesis by Z‐100‐induced IFN‐γ. IFN‐γ acts as a key cytokine in anti‐tumor activities of Z‐100.

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Hormonal changes following tumor transplantation: Factors increasing corticosterone and the relationship of corticosterone to tumor‐induced anti‐inflammation

Cited by 16 publications

References 12 publications

Adrenal enlargement and failure of suppression of circulating cortisol by dexamethasone in patients with malignancy

Adrenal enlargement and failure of suppression of circulating cortisol by dexamethasone in patients with malignancy

Catecholamine, Indoleamine and Corticosteroid Responses in Mice Bearing Tumors

Anti‐Tumor Mechanism of Z‐100, an Immunomodulatory Arabinomannan Extracted from Mycobacterium tuberculosis Strain Aoyama B, on Pulmonary Metastases of B16F10 Melanoma: Restoration of Helper T Cell Responses via Suppression of Glucocorticoid‐Genesis

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