ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Immune-induced fever is mediated by IL-6 receptors on brain endothelial cells coupled to STAT3-dependent induction of brain endothelial prostaglandin synthesis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
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- PGE2 modulation of stimulus valence directs zebrafish behavioral fever.bioRxiv : the preprint server for biology · 2026Article
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- Therapeutic potential of exerkines in neurodegenerative and mental disorders: a narrative review.Frontiers in physiology · 2026Review
- Effects of environment and globalization on the double and triple burdens of infection symptoms among under-five children across low-middle income countries using machine learning algorithms.Infectious diseases of poverty · 2025Article
- Plasma biomarkers for monitoring muscle function and physical performance decline in older adults: A 2-year longitudinal study.The journal of nutrition, health & aging · 2025Article
- Partial depletion of circulating neutrophil granulocytes in mice exacerbates the inflammatory response and hypothermia during LPS induced severe systemic inflammation.Frontiers in immunology · 2025Article
- Mechanisms of Acetate in Alleviating SETDB1-Linked Neuroinflammation and Cognitive Impairment in a Mouse Model of OSA.Journal of inflammation research · 2025Article
- Adolescent intermittent ethanol (AIE) sensitized fever in male Sprague Dawley rats exposed to poly I:C in adulthood.Brain, behavior, and immunity · 2024Article
- Muscle-brain crosstalk mediated by exercise-induced myokines - insights from experimental studies.Frontiers in physiology · 2024Review
- Prostaglandin ETemperature (Austin, Tex.) · 2024Review
- Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.Pharmaceutical biology · 2023Article
- Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair.Journal of neurotrauma · 2023Review
- Review
- Prostaglandin EDNA and cell biology · 2023Article
- Immune responses in mildly versus critically ill COVID-19 patients.Frontiers in immunology · 2023Review
- Prostaglandin production in brain endothelial cells during the initiation of fever.Communicative & integrative biology · 2023Article
- Systemic Lipopolysaccharide Challenge Induces Inflammatory Changes in Rat Dorsal Root Ganglia: An Ex Vivo Study.International journal of molecular sciences · 2022Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytokine IL-6, which is released upon peripheral immune challenge, is critical for the febrile response, but the mechanism by which IL-6 is pyrogenic has remained obscure. Here we generated mice with deletion of the membrane bound IL-6 receptor α (IL-6Rα) on neural cells, on peripheral nerves, on fine sensory afferent fibers, and on brain endothelial cells, respectively, and examined its role for the febrile response to peripherally injected lipopolysaccharide. We show that IL-6Rα on neural cells, peripheral nerves, and fine sensory afferents are dispensable for the lipopolysaccharide-induced fever, whereas IL-6Rα in the brain endothelium plays an important role. Hence deletion of IL-6Rα on brain endothelial cells strongly attenuated the febrile response, and also led to reduced induction of the prostaglandin synthesizing enzyme Cox-2 in the hypothalamus, the temperature-regulating center in the brain, as well as reduced expression of SOCS3, suggesting involvement of the STAT signaling pathway. Furthermore, deletion of STAT3 in the brain endothelium also resulted in attenuated fever. These data show that IL-6, when endogenously released during systemic inflammation, is pyrogenic by binding to IL-6Rα on brain endothelial cells to induce prostaglandin synthesis in these cells, probably in concerted action with other peripherally released cytokines.
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