ArticleProceedings of the National Academy of Sciences of the United States of America2000
Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 377 citations in OpenAlex.
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- Interleukin-2 Transiently Inhibits Pulsatile Growth Hormone Secretion in Young but not Older Healthy Men.The Journal of clinical endocrinology and metabolism · 2021Trial
- The NRF2 stimulating agent, tin protoporphyrin, activates protective cytokine pathways in healthy human subjects and in patients with chronic kidney disease.Physiological reports · 2020Trial
- Trial
- Human models of low-grade inflammation: bolus versus continuous infusion of endotoxin.Clinical and vaccine immunology : CVI · 2007Trial
- Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle.The Journal of physiology · 2004Trial
- Perioperative Anxiety in Adults: A Narrative Review of Pathophysiology, Assessment, and Multimodal Management Strategies.Healthcare (Basel, Switzerland) · 2026Review
- Ventromedial hypothalamus IL-6 signaling mediates the excessive aggressive behavior induced by late-gestational sleep deprivation in male mice.Behavioral and brain functions : BBF · 2026Article
- Molecular Mechanisms of Negative Effect of Systemic Lupus Erythematosus on Oogenesis and Meiotic Processes in Oocytes.International journal of molecular sciences · 2026Review
- Systemic inflammatory mediators and neurodevelopmental outcomes in term infants: a retrospective cohort study.BMC pediatrics · 2026Article
- Exercise Duration Modulates Cortisol Release and Chronic Cortisol Exposure Jeopardises T Cell Effector Functions.Immunology · 2026Article
- Acupuncture modulates the microbiota-gut-brain axis to treat irritable bowel syndrome: a mechanistic exploration.Frontiers in neuroscience · 2026Review
- Towards an Integrative Account of Potential Mechanisms Mediating the Path From Sleep Dysfunction to Hallucinations.Schizophrenia bulletin · 2025Review
- Modulation of neuroimmune cytokine networks by antidepressants: implications in mood regulation.Translational psychiatry · 2025Review
- Association between body roundness index and sleep disorder: the mediating role of depression.BMC psychiatry · 2025Article
- Novel insights and an updated review of metabolic syndrome in immune-mediated organ transplant rejection.Frontiers in immunology · 2025Review
- The immunology of sickness metabolism.Cellular & molecular immunology · 2024Review
- Corticotropin-releasing hormone deficiency results in impaired analgesic response during CFA-induced inflammation.Hormones (Athens, Greece) · 2024Article
- Prenatal maternal Inflammation, childhood cognition and adolescent depressive symptoms.Brain, behavior, and immunity · 2024Article
- Complement C5a Receptor Signaling Alters Stress Responsiveness and Modulates Microglia Following Chronic Stress Exposure.Biological psychiatry global open science · 2024Article
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Glucocorticoids play a critical role in control of the cytokine response after immune challenge. Conversely, cytokines modulate glucocorticoid production by the hypothalamic-pituitary-adrenal axis. To define the potency and mechanism of interleukin-6 (IL-6) for augmentation of adrenal function, we exploited mice deficient in corticotropin-releasing hormone (CRH), IL-6, or both. Mice deficient in CRH action demonstrate severely impaired glucocorticoid production in response to psychological and metabolic challenge, but near normal responses to stressors that activate the immune system. In this paper, we demonstrate that IL-6 is essential for activation of the hypothalamic-pituitary-adrenal axis during immunological challenge in the absence of hypothalamic input from CRH. IL-6 receptors are present on pituitary corticotrophs and adrenocortical cells, consistent with the ability of IL-6 to bypass CRH in augmentation of adrenal function. Plasma corticosterone levels after bacterial lipopolysaccharide injection in mice deficient in CRH or IL-6 were significantly lower than in wild-type mice but significantly greater than in mice deficient in both CRH and IL-6. A second model of immune system activation using 2C11, an antibody to the T cell receptor, demonstrated a normal corticosterone response in mice deficient in CRH or IL-6, but a markedly decreased response in mice deficient in both CRH and IL-6. Surprisingly, the relative contribution of IL-6 for modulation of the adrenal response to stress is greater in female than in male mice. This gender-specific difference in IL-6 action in mice suggests the utility of further analysis of IL-6 in determining the female predominance seen in many human inflammatory/autoimmune diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.