Acute adrenocortical stimulation by recombinant gamma interferon in human controls

Holsboer, Florian; Stalla, G. K.; Bardeleben, U. von; Hammann, Klaus P.; Müller, H.; Müller, Otto

doi:10.1016/0024-3205(88)90617-0

Cited by 61 publications

(18 citation statements)

References 8 publications

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“…Prolactin levels were found unmodifi ed [5,8,9] , stimulated [9][10][11] or decreased after IFN treatment [12][13][14][15][16] . A similar picture was obtained for ACTH (stimulation [5, 8, 9, 17-19] , inhibition [12] , no effect [2, [20][21][22] ) or for growth hormone (GH; stimulation [5,8,9,23,24] , inhibition [12, 14-16] , no effect [2, 9] ).…”

mentioning

confidence: 60%

Effect of Interferon-γ Treatment on 24-Hour Variations in Plasma ACTH, Growth Hormone, Prolactin, Luteinizing Hormone and Follicle-Stimulating Hormone of Male Rats

Cano

Cardinali²,

Jiménez³

et al. 2005

Neuroimmunomodulation

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Objective: Interferon-γ (IFN-γ) is a cytokine produced by T helper cells on antigenic challenge that may affect the release of several pituitary hormones. However, in vitro or in vivo studies have yielded disparate results with stimulatory, inhibitory or absent effects of IFN on pituitary hormone release. One of the reasons for these discrepancies could be that hormone changes were commonly assessed at a single time point in the day-night cycle. In this study we measured the circadian pattern of plasma ACTH, growth hormone (GH), prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 6 different time points within a 24-hour cycle in adult male Wistar rats. Methods: Groups of 6–8 rats kept under light from 08:00 to 20:00 h daily received 5 daily injections intraperitoneally of human IFN-γ (10⁵ IU/kg body weight) or saline at 08:30 h. Plasma ACTH, GH, prolactin, LH and FSH levels were measured by a homologous specific double antibody RIA. Results: A factorial ANOVA for main effects indicated a significant 43% increase of circulating prolactin in IFN-γ-treated rats. Time of day changes were significant for the five hormones examined and these diurnal variations became altered by IFN-γ administration, with a phase advance of ACTH peak, a suppression of the rest phase peak of GH, the appearance of a second peak of prolactin at an early phase of daily photoperiod, and the blunting of the 24-hour variations of plasma FSH. Conclusion: The data point out an effect of IFN-γ on the mechanisms responsible for the circadian organization of pituitary hormone release.

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confidence: 60%

Effect of Interferon-γ Treatment on 24-Hour Variations in Plasma ACTH, Growth Hormone, Prolactin, Luteinizing Hormone and Follicle-Stimulating Hormone of Male Rats

Cano

Cardinali²,

Jiménez³

et al. 2005

Neuroimmunomodulation

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“…caused by IFN-a-induced fever or through other mediators. Holsboer et al [19], for instance, interpreted their observation of IFN-«-induced stimulation of the HPA axis in this way. A fa vorite candidate for a mediator substance involved in the mediation of the IFN-a effects would be the generation of other ILs by IFN-a, such as IL-1 and IL-6, which have both a pyrogenic and ACTH-releasing activity.…”

Section: Discussionmentioning

confidence: 99%

Interferon-α Stimulates the Hypothalamic- Pituitary-Adrenal Axis in vivo and in vitro

et al. 1993

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The successful therapeutic use of interferon-α (IFN-α) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-α therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-α a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-α therapy, no significant stimulation of the HPA axis occurred after administration of IFN-α. IFN-α-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-α treatment for 3 weeks. To determine the exact locus of the IFN-α action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-α at concentrations of 5 × 10^–8M or 10^–7M respectively. In contrast, no direct IFN-α effect on pituitary ACTH secretion could be observed in vitro. It is concluded that IFN-α stimulates the HPA axis. The locus of action seems to be the hypothalamus, as well as the adrenal glands.

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“…Interleukin-2, interferon-y or -a; have been shown to stimulate the secretion o f cortisol in man (3-7). Ef fects o f the secretion o f adrenocorticotrophic hormone (ACTH) have been registered in two studies using interferon-y [5,6] which did not significantly interfere with the release o f ACTH. Moreover, from the data reported so far it cannot be excluded that stimulation o f the HPA axis by cyto kines is due to fever or other flu-like symptoms which may occur after administration o f cytokines [8].…”

mentioning

confidence: 99%

Interferon-Alpha-2-Induced Stimulation of ACTH and Cortisol Secretion in Man

Müller

Hammes²,

Hiemke³

et al. 1991

Neuroendocrinology

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Short-term effects of interferon-α₂ on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol were measured in man in relation to interferon absorption. Interferon-α₂ was given subcutaneously at a dose of 3 × 10⁶ IU at 17.00 h to 2 female and 5 male patients who suffered from chronic hepatitis B infection and who had not previously been treated with interferon. Plasma levels of ACTH, cortisol and interferon-α were determined at 30-min intervals between 16.00 and 24.00 h. In each patient a similar cortisol, ACTH and interferon-α profile was determined on a day, when no interferon-α treatment was given. Interferon-α plasma levels peaked around 21.30 h, i.e. 4.7 h after injection. In each patient ACTH and cortisol levels were increased. As calculated from the areas under the curves, ACTH release was increased by an average of 332% (maxima at about 22.00 h, i.e. 5.2 h post injection); cortisol release was increased by an average of 311% (maxima at about 23.00 h, 5.8 h post injection). These actions were not related to side effects like fever or other flu-like symptoms. Our findings confirm that in man as in animals interferon-α₂ can act as a mediator between the immune and endocrine system.

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Acute adrenocortical stimulation by recombinant gamma interferon in human controls

Cited by 61 publications

References 8 publications

Effect of Interferon-γ Treatment on 24-Hour Variations in Plasma ACTH, Growth Hormone, Prolactin, Luteinizing Hormone and Follicle-Stimulating Hormone of Male Rats

Effect of Interferon-γ Treatment on 24-Hour Variations in Plasma ACTH, Growth Hormone, Prolactin, Luteinizing Hormone and Follicle-Stimulating Hormone of Male Rats

Interferon-α Stimulates the Hypothalamic- Pituitary-Adrenal Axis in vivo and in vitro

Interferon-Alpha-2-Induced Stimulation of ACTH and Cortisol Secretion in Man

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