Effects of cytokines on the pituitary-adrenal axis in cancer patients

W. E. Nolten, D. Goldstein, M. Lindstrom, M. V. McKenna, I. H. Carlson, D. L. Trump, J. Schiller, E. C. Borden, E. N. Ehrlich

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-β (IFN-β(ser)), 90 or 450 x 106 IU, IFN-γ, 0.1-100 x 106 IU, or TNF 125-275 μg/m2. Sixty to 120 min after IFN-β(ser) injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-β(ser) administration. IFN-γ ≥30 x 106 IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

Original languageEnglish (US)
Pages (from-to)349-357
Number of pages9
JournalJournal of Interferon Research
Volume13
Issue number5
StatePublished - 1993

Fingerprint

Interferons
Cytokines
Hydrocortisone
Neoplasms
Adrenocorticotropic Hormone
Tumor Necrosis Factor-alpha
Interleukins
Prolactin
Growth Hormone
Injections
Pituitary Hormones
Glucocorticoids
Immune System
Lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Nolten, W. E., Goldstein, D., Lindstrom, M., McKenna, M. V., Carlson, I. H., Trump, D. L., ... Ehrlich, E. N. (1993). Effects of cytokines on the pituitary-adrenal axis in cancer patients. Journal of Interferon Research, 13(5), 349-357.

Effects of cytokines on the pituitary-adrenal axis in cancer patients. / Nolten, W. E.; Goldstein, D.; Lindstrom, M.; McKenna, M. V.; Carlson, I. H.; Trump, D. L.; Schiller, J.; Borden, E. C.; Ehrlich, E. N.

In: Journal of Interferon Research, Vol. 13, No. 5, 1993, p. 349-357.

Research output: Contribution to journalArticle

Nolten, WE, Goldstein, D, Lindstrom, M, McKenna, MV, Carlson, IH, Trump, DL, Schiller, J, Borden, EC & Ehrlich, EN 1993, 'Effects of cytokines on the pituitary-adrenal axis in cancer patients', Journal of Interferon Research, vol. 13, no. 5, pp. 349-357.
Nolten WE, Goldstein D, Lindstrom M, McKenna MV, Carlson IH, Trump DL et al. Effects of cytokines on the pituitary-adrenal axis in cancer patients. Journal of Interferon Research. 1993;13(5):349-357.
Nolten, W. E. ; Goldstein, D. ; Lindstrom, M. ; McKenna, M. V. ; Carlson, I. H. ; Trump, D. L. ; Schiller, J. ; Borden, E. C. ; Ehrlich, E. N. / Effects of cytokines on the pituitary-adrenal axis in cancer patients. In: Journal of Interferon Research. 1993 ; Vol. 13, No. 5. pp. 349-357.
@article{81f7f54c11aa4e17800f2ba9d5d63e80,
title = "Effects of cytokines on the pituitary-adrenal axis in cancer patients",
abstract = "Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-β (IFN-β(ser)), 90 or 450 x 106 IU, IFN-γ, 0.1-100 x 106 IU, or TNF 125-275 μg/m2. Sixty to 120 min after IFN-β(ser) injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-β(ser) administration. IFN-γ ≥30 x 106 IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.",
author = "Nolten, {W. E.} and D. Goldstein and M. Lindstrom and McKenna, {M. V.} and Carlson, {I. H.} and Trump, {D. L.} and J. Schiller and Borden, {E. C.} and Ehrlich, {E. N.}",
year = "1993",
language = "English (US)",
volume = "13",
pages = "349--357",
journal = "Journal of Interferon Research",
issn = "0197-8357",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - Effects of cytokines on the pituitary-adrenal axis in cancer patients

AU - Nolten, W. E.

AU - Goldstein, D.

AU - Lindstrom, M.

AU - McKenna, M. V.

AU - Carlson, I. H.

AU - Trump, D. L.

AU - Schiller, J.

AU - Borden, E. C.

AU - Ehrlich, E. N.

PY - 1993

Y1 - 1993

N2 - Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-β (IFN-β(ser)), 90 or 450 x 106 IU, IFN-γ, 0.1-100 x 106 IU, or TNF 125-275 μg/m2. Sixty to 120 min after IFN-β(ser) injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-β(ser) administration. IFN-γ ≥30 x 106 IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

AB - Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-β (IFN-β(ser)), 90 or 450 x 106 IU, IFN-γ, 0.1-100 x 106 IU, or TNF 125-275 μg/m2. Sixty to 120 min after IFN-β(ser) injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-β(ser) administration. IFN-γ ≥30 x 106 IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

UR - http://www.scopus.com/inward/record.url?scp=0027787074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027787074&partnerID=8YFLogxK

M3 - Article

VL - 13

SP - 349

EP - 357

JO - Journal of Interferon Research

JF - Journal of Interferon Research

SN - 0197-8357

IS - 5

ER -