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 - 1993/10
Y1 - 1993/10
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-βser), 90 or 450 x 106 IU, IFN-γ, 0.1–100 × 106 IU, or TNF 125–275 μg/m2. Sixty to 120 min after IFN-βser 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-βser administration. IFN-γ ≥30 × 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-βser), 90 or 450 x 106 IU, IFN-γ, 0.1–100 × 106 IU, or TNF 125–275 μg/m2. Sixty to 120 min after IFN-βser 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-βser administration. IFN-γ ≥30 × 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.
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U2 - 10.1089/jir.1993.13.349
DO - 10.1089/jir.1993.13.349
M3 - Article
C2 - 8301155
AN - SCOPUS:0027787074
SN - 0197-8357
VL - 13
SP - 349
EP - 357
JO - Journal of Interferon Research
JF - Journal of Interferon Research
IS - 5
ER -