The DOI matches its Crossref record; 103 of the 103 references it cites were found in a registry or an index.
The Pathophysiologic Roles of Interleukin-6 in Human Disease
Abstract
Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.
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In the citing paper
“These autoimmune diseases are associated with dysregulated production of IL-6 in humans (41–43) and impaired activation of the HPA axis in both humans (44) and animal models (1).”
From Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation (2000) · cites this paper as [43]
In the citing paper
“In this study, we provide evidence of one core pathway behind the diverse health risks associated with caregiving and other chronic stressors: overproduction of IL-6, a key proinflammatory cytokine that appears to enhance morbidity and mortality among older adults (10).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [10]
In the citing paper
“overproduction of IL-6, a key proinflammatory cytokine that appears to enhance morbidity and mortality among older adults (10).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [10]
In the citing paper
“IL-6 is associated with a variety of age-related illnesses (10, 13-15, 38).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [10]
In the citing paper
“However, with increasing recognition that inflammation is a key pathogenic mechanism in many infectious, autoimmune, cardiovascular, and psychiatric diseases (11–13), the adequacy of this explanation has been called into question (14–15).”
From A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling (2008) · cites this paper as [12]
In the citing paper
“This profile suggests a scenario in which long-term stress brings about a functional resistance to glucocortioid signal transduction in monocytes, which reduces inhibition of NF-κB and EGR1, and thereby fosters the kind of pro-inflammatory dynamics that ultimately promote chronic diseases, including diabetes, coronary disease, autoimmune disorders, chronic infections, and some cancers (11–13).”
From A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling (2008) · cites this paper as [12]
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Self-citation
Metadata
- Authors
- Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C., & Chrousos, G. P.
- Affiliations
- An edited summary of a Clinical Staff Conference held on 13 March 1996 at the National Institutes of Health, Bethesda, Maryland.
- Corresponding author
- Papanicolaou, Dimitris A.
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 1998-01-15
- Volume
- 128
- Issue
- 2
- Pages
- 127-137
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W1985953874
- Cited by
- 1,146
- References
- 103
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 17 · 2023: 20 · 2022: 22 · 2021: 29 · 2020: 23 · 2019: 17 · 2018: 27 · 2017: 25 · 2016: 38 · 2015: 29 · 2014: 50 · 2013: 37 · 2012: 60
- FWCI
- 18.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- interleukin-6, inflammatory cytokines, hypothalamic-pituitary-adrenal axis, glucocorticoid negative feedback, growth hormone secretion, serum lipids, fever, vasopressin, rheumatoid arthritis, sex steroids, osteoporosis, bone resorption, aging, chronic stress
- MeSH terms
- Aging, Autoimmune Diseases, Bone Diseases, Endocrine System, Female, Humans, Immune System, Inflammation, Interleukins, Male, Osteoporosis, United States
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 ›
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