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]
Citations
Cites
Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
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Self-citationImpaired immune and acute-phase responses in interleukin-6-deficient mice
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Self-citationIncreased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6
Jilka, R. L., Hangoc, G., Girasole, G., Passeri, G., Williams, D. C., Abrams, J. S., Boyce, B. F., Broxmeyer, H. E., & Manolagas, S. C. (1992) · Science · doi:10.1126/science.1621100 · Cited by 1,440
Self-citationInterleukin-6 family of cytokines and gp130.
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“Because it innervates many immune organs, such as the spleen and the thymus, the autonomic nervous system interacts directly with the immune system (33, 34).”
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Cited by
Sorted by citations
Psychological stress and the human immune system: a meta-analytic study of 30 Years of inquiry
Segerstrom, S. C., & Miller, G. E. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.4.601 · Cited by 3,334
Stress and disorders of the stress system
Chrousos, G. P. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.106 · Cited by 3,215
Self-citationElevated C-reactive protein levels in overweight and obese adults
Visser, M. (1999) · JAMA · doi:10.1001/jama.282.22.2131 · Cited by 2,494
Ridker, P. M., Rifai, N., Stampfer, M. J., & Hennekens, C. H. (2000) · Circulation · doi:10.1161/01.cir.101.15.1767 · Cited by 2,429
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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
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- Papanicolaou, D. A., Wilder, R. L., Manolagas, S. C., & Chrousos, G. P. (1998). The Pathophysiologic Roles of Interleukin-6 in Human Disease. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-128-2-199801150-00009
