ArticleThe Journal of experimental medicine1994
Defective inflammatory response in interleukin 6-deficient mice.
Article in The Journal of experimental medicine, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05997641 (A Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered DF-003 Following Single), which is not on this map. Cited by 142 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Orally Administered DF-003 Following Single (Part 1) and Multiple (Part 2) Ascending Doses in Healthy Subjects
Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 529 citations in OpenAlex.
- Vitamin D and Ocular Diseases: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- The acute phase protein response in patients receiving subcutaneous IL-6.Clinical and experimental immunology · 1995Trial
- Superior inflammatory response and MASH progression inFrontiers in immunology · 2026Article
- Elevated Interleukin-6 Is Associated with an Increased Risk of Long-Term Arteriovenous Fistula Failure for Dialysis.Journal of clinical medicine · 2025Article
- Saccharomyces yeast postbiotics mitigate mucosal damages from F18Animal microbiome · 2024Article
- Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis, the first Chinese experience.Pediatric rheumatology online journal · 2024Article
- How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling.Immunologic research · 2024Article
- Characteristics of cytokines/chemokines associated with disease severity and adverse prognosis in COVID-19 patients.Frontiers in immunology · 2024Article
- Botanical formulation HX110B ameliorates PPE-induced emphysema in mice via regulation of PPAR/RXR signaling pathway.PloS one · 2024Article
- Interleukin-6 in COVID-19 Severity Stratification.Tanaffos · 2023Article
- Role of interleukin-6-mediated inflammation in the pathogenesis of inflammatory bowel disease: focus on the available therapeutic approaches and gut microbiome.Journal of cell communication and signaling · 2023Review
- Oral Administration of Vitamin D3 Prevents Corneal Damage in a Knock-Out Mouse Model of Sjögren's Syndrome.Biomedicines · 2023Article
- Efficacy and safety of canakinumab as a second line biologic after tocilizumab treatment failure in children with systemic juvenile idiopathic arthritis: A single-centre cohort study using routinely collected health data.Frontiers in pediatrics · 2023Article
- Effect and Mechanism of Herbal Medicines on Cisplatin-Induced Anorexia.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Prospective self- and informant-personality associations with inflammation, health behaviors, and health indicators.Health psychology : official journal of the Division of Health Psychology, American Psychological Association · 2022Article
- Review
- Using different machine learning models to classify patients into mild and severe cases of COVID-19 based on multivariate blood testing.Journal of medical virology · 2022Article
- Interleukin-6 is dispensable in pituitary normal development and homeostasis but needed for pituitary stem cell activation following local injury.Frontiers in endocrinology · 2022Article
- Interleukin-6 in blood and bronchoalveolar lavage fluid of hospitalized children with community-acquired pneumonia.Frontiers in pediatrics · 2022Article
- Elevated Levels of Pleiotropic Interleukin-6 (IL-6) and Interleukin-10 (IL-10) are Critically Involved With the Severity and Mortality of COVID-19: An Updated Longitudinal Meta-Analysis and Systematic Review on 147 Studies.Biomarker insights · 2022Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic and localized inflammation elicit a number of host responses which include fever, cachexia, hypoglycemia, and major changes in the concentration of liver plasma proteins. Interleukin 6 (IL-6) is considered an important mediator of the inflammatory response, together with IL-1 and tumor necrosis factor alpha (TNF-alpha). The purpose of this study was to unequivocally determine the role of IL-6 in these phenomena making use of IL-6-deficient mice that we have recently generated by gene targeting. We report here that in the absence of IL-6, mice are unable to mount a normal inflammatory response to localized tissue damage generated by turpentine injection. The induction of acute phase proteins is dramatically reduced, mice do not lose body weight and only suffer from mild anorexia and hypoglycemia. In contrast, when systemic inflammation is elicited through the injection of bacterial lipopolysaccharide (LPS), these parameters are altered to the same extent both in wild-type and IL-6-deficient mice, demonstrating that under these conditions IL-6 function is dispensable. Moreover, we show that LPS-treated IL-6-deficient mice produce three times more TNF-alpha than wild-type controls, suggesting that increased TNF-alpha production might be one of the compensatory mechanisms through which a normal response to LPS is achieved in the absence of IL-6. We also show that corticosterone is normally induced in IL-6-deficient mice, demonstrating that IL-6 is not required for the activation of the hypothalamic-pituitary-adrenal axis. Our results reinforce the idea that different patterns of cytokines are involved in systemic and localized tissue damage, and identify IL-6 as an essential mediator of the inflammatory response to localized inflammation.
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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.