The DOI matches its Crossref record.
Interleukin-6 stimulates the hypothalamus-pituitary-adrenocortical axis in man.
Abstract
A recent study in humans, animal studies, and in vitro data have suggested that interleukin-6 (IL-6) stimulates the secretory activity of the hypothalamus-pituitary-adrenocortical (HPA) axis. In a phase II study, one female and six male patients with metastatic renal cell carcinoma received IL-6 to evaluate a possible antitumor effect of IL-6. This offered the possibility of investigating the influence of IL-6 on the HPA axis in man. The subjects were studied 1 day before, on day 1, and on day 21 of IL-6 therapy (150 micrograms administered sc every day at 0900 h). Blood samples were taken at 0900, 1100, 1300, 1600, and 2000 h the day before, on day 1 of IL-6 therapy, 24 h after the first IL-6 injection, and on day 21 of IL-6 treatment. Plasma ACTH and cortisol levels promptly followed the rise of IL-6, which peaked 4 h after administration. They were significantly (P < 0.05) higher at 1100 and 1300 h on day 1 of IL-6 therapy compared with the corresponding plasma levels the day before IL-6 treatment. Cortisol concentrations remained significantly increased at 1600 and 2000 h after IL-6 administration. Twenty-four hours after the first IL-6 administration, IL-6, ACTH, and cortisol levels had reached preinjection values. Although plasma cortisol levels were similar on days 1 and 21, ACTH levels were lower on day 21 (than on day 1), but significantly elevated at 1100 h compared with levels on the day before the first IL-6 injection. Results confirming the very recent data of another study demonstrate a stimulating effect of IL-6 on the HPA axis in man. They support the notion that IL-6 is one of the cytokines involved in the interaction between the immune system and the HPA axis.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Citations
Cited by
Sorted by citations
Items 101–139 of 139
Gheorghe-Milea, A., Stănoiu-Pînzariu, O., & Georgescu, C. E. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1563967 · Cited by 8
The autonomic and neurohumoral response to critical illness
Goldstein, B., & Woolf, P. D. (1996) · Clinical Intensive Care · doi:10.3109/tcic.7.6.297.307 · Cited by 6
Cytokines and the adrenal cortex: basic research and clinical implications
Bornstein, S. R. (2000) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/00060793-200006000-00005 · Cited by 6
Self-citationConstruction of a risk signature for adrenocortical carcinoma using immune-related genes
Fu, Y., Sun, S., Bi, J., & Kong, C. (2020) · Translational Andrology and Urology · doi:10.21037/tau-20-485 · Cited by 6
The Different Paths That Lead to Hypotonic Hyponatremia, and a Safe Approach to Treatment
Imbriano, L. J., Grant, C. D., & Masani, N. N. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm14010092 · Cited by 5
“Studies by Spath-Schwalbe et al. have suggested that interleukin 6 stimulates the secretory activity of the hypothalamus–pituitary–adrenocortical axis (HPA), with rapid increases in plasma adrenocorticotropic hormone (ACTH) and cortisol levels after injection of IL-6 [11].”
Adaptation of the Porcine Pituitary Transcriptome, Spliceosome and Editome during Early Pregnancy
Makowczenko, K. G., Jastrzebski, J., Kieżun, M., Paukszto, Ł., Dobrzyń, K., Smolińska, N., & Kamiński, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065946 · Cited by 5
Pavlov, V. A., Ulloa, L., & Metz, C. N. (2010) · Neuroimmune biology · doi:10.1016/s1567-7443(10)70027-2 · Cited by 7
Boieriu, A. M., Luca, C. D., Neculoiu, C. D., et al. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1480925 · Cited by 4
Interleukin-2 drives cortisol secretion in an age-, dose-, and body composition-dependent way
Roelfsema, F., Liu, P. Y., Yang, R. J., Takahashi, P. Y., & Veldhuis, J. D. (2020) · Endocrine Connections · doi:10.1530/ec-20-0211 · Cited by 5
Adrenocortical Function and Inflammatory Response During Sepsis
Marx, C., Höffken, G., & Petros, S. (2002) · Critical Care Medicine · doi:10.1097/00003246-200208000-00064 · Cited by 4
The systemic adrenal stress response in severe sepsis and critical illness
Marx, C. (2005) · Clinical Intensive Care · doi:10.3109/09563070500061422 · Cited by 5
Neuroendocrinology and the Immune Response
Vrezas, I., Ziegler, C. G., Krug, A. W., & Bornstein, S. R. (2007) · Neuroimmune biology · doi:10.1016/s1567-7443(07)00214-1 · Cited by 3
Self-citationThe role of interferon-alpha in the regulation of sleep
Born, J., & Späth‐Schwalbe, E. (1999) · Key topics in brain research · doi:10.1007/978-3-7091-6404-4_14 · Cited by 3
Self-citationHarvey, A. K. (2016) · Journal of Rheumatic Diseases and Treatment · doi:10.23937/2469-5726/1510033 · Cited by 2
“Notably, a concurrent increase in adrenal proinflammatory IL-6 expression, Il6, was measured in the Il10-/- AIA group (Figure 5C, t10 = 3.55, p 0.01), compared to the WT-AIA group.”
BackgroundInfluentialRiesenzellarteriitis: Aktuelle Erkenntnisse zu Epidemiologie, Pathogenese, Diagnostik und Therapie
Keyßer, G. (2019) · Aktuelle Rheumatologie · doi:10.1055/a-0968-6782 · Cited by 2
Hormonal Changes During and After Cardiac Surgery
Maggio, M., Cattabiani, C., & Ceda, G. P. (2011) · Springer eBooks · doi:10.1007/978-1-4419-0892-6_25 · Cited by 2
“The phenomenon of dissociated cortisol and ACTH levels may be the result of changes in adrenal sensitivity, alterations in glucocorticoid receptor function, ACTH independent mechanisms of steroidogenesis, and elevations of other peptides and cytokines involved in ACTH and CRH release [104, 105 ].”
BackgroundEffects of cytokines on human EEG and sleep
Jan Born, A., & Späth‐Schwalbe, E. (1997) · Key topics in brain research · doi:10.1007/978-3-7091-6870-7_14 · Cited by 2
Self-citationIntérêts du Dosage du Cortisol Plasmatique Chez Des Cyclistes Élite
Guinot, M., Duclos, M., Souberbielle, J., Mégret, A., & Bouc, Y. L. (2005) · Revue Francophone des Laboratoires · doi:10.1016/s1773-035x(05)80150-9 · Cited by 1
Cronin, S. J. F., Tejada, M. A., Song, R., Laval, K., Cikes, D., Ji, M., Brai, A., Stadlmann, J., Novatchikova, M., Perlot, T., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.09.539956 · Cited by 2
“These previous studies, combined with our data, indicate that the source of IL‐6 may be the injured DRG neurons or surrounding satellite glia cells, which can then activate the HPA axis and corticosterone‐dependent stress response (KAPCALA et al., 1995; Späth‐Schwalbe et al., 1994) to cause the thymic atrophy (Ansari…”
BackgroundResultA Rare Case of Interleukin-6-producing Adrenocortical Carcinoma Presenting with a Persistent Fever
Oguni, K., Goshima, Y., Tatsushima, K., Hayashida, M., Urakami, S., Ito, S., Yamazaki, Y., Sasano, H., Takeuchi, Y., & Takeshita, A. (2025) · Internal Medicine · doi:10.2169/internalmedicine.4599-24 · Cited by 1
“Previous studies re-ported that daily administration of IL-6 increased both ACTH and cortisol levels, and although cortisol levels remained elevated over time, ACTH responses were attenuated (8, 9).”
Inflammatory Mediators Affect the Autonomic Nervous System
Straub, R. H., Kees, M. G., Janele, D., Pongratz, G., Schölmerich, J., & Härle, P. (2007) · Neuroimmune biology · doi:10.1016/s1567-7443(07)00215-3 · Cited by 1
Könemann, S., Dörr, M., & Felix, S. B. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-803267-1.00028-4 · Cited by 2
Roelfsema, F., Yang, R. J., & Veldhuis, J. D. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab484 · Cited by 1
Pathogenesis and Neuroendocrine Immunology
Straub, R. H. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-803321-0.00002-1 · Cited by 1
Samra, J. S., & Summers, L. K. M. (1997) · Annals of Surgery · doi:10.1097/00000658-199701000-00026
Inflammatory Mediator Action on the Anterior Pituitary Gland
Giacomini, D., Acuña, M., Nagashima, A. C., et al. (2007) · Neuroimmune biology · doi:10.1016/s1567-7443(07)00213-x
Ha, K. (2014) · Brandeis Institutional Repository
Brain Stem Involvement in Immune and Aversive Challenge
Paues, J. (2006) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
The Effect of Manipulating the IL-6 Response to Exercise on Biomarkers and Exercise Performance
Walshe, I. H. (2012) · Northumbria Research Link (Northumbria University)
Minter, R. M., Wessels, F. J., & Moldawer, L. L. (2001) · Elsevier eBooks · doi:10.1016/b978-012655330-7/50069-1
Systemic Manifestations of Cancer and Paraneoplastic Syndromes
Desai, J., Gold, M., Fullerton, S., et al. (2001) · doi:10.1007/978-1-4613-1099-0_31
Hussey, R. C. (2013) · Trinity's Access to Research Output (TARA) (Trinity College Dublin)
The role of toll-like receptors in the adrenal gland
Tran, T. H. N. (2009) · Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt)
Zytokine in der pädiatrischen Rheumatologie
Horneff, G. (2021) · Springer Reference Medizin · doi:10.1007/978-3-662-60411-3_6-1
Frey, O., Kamradt, T., Wagner, N., Tarakhovsky, A., Roth, J., Haas, J., Horneff, G., Zepp, F., & Dannecker, G. E. (2007) · Springer eBooks · doi:10.1007/978-3-540-32815-5_2
(2015) · Elsevier eBooks · doi:10.1016/b978-0-12-803321-0.09996-1
Фокин, В. Ф., Шабалина, А. А., Пономарева, Н. В., Medvedev, R. B., Лагода, О. В., & Танашян, М. М. (2023) · Zhurnal «Patologicheskaia fiziologiia i eksperimental`naia terapiia» · doi:10.25557/0031-2991.2023.03.51-57
Straub, R. H. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-803321-0.00003-3
Metadata
- Authors
- Späth-Schwalbe, E., Born, J., Schrezenmeier, H., Bornstein, S. R., Stromeyer, P., Drechsler, S., Fehm, H. L., & Porzsolt, F.
- Affiliations
- Universität Ulm (DE)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1994-10
- Volume
- 79
- Issue
- 4
- Pages
- 1212-1214
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2005611582
- Cited by
- 145
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- interleukin-6, ACTH, cortisol, metastatic renal cell carcinoma, cytokine therapy
- MeSH terms
- Adrenal Cortex, Adrenocorticotropic Hormone, Circadian Rhythm, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Osmolar Concentration, Pituitary-Adrenal System, Recombinant Proteins, Interleukin-6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review