ArticleThe Journal of clinical investigation1997
Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 2 syntheses or guidelines pooled it, 314 citations in OpenAlex.
- Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies.European journal of internal medicine · 2021Pooled it
- Sirukumab: A Potential Treatment for Mood Disorders?Advances in therapy · 2017Pooled it
- Breast cancer survivors' typhoid vaccine responses: Chemotherapy, obesity, and fitness make a difference.Brain, behavior, and immunity · 2022Trial
- Randomized trial of the effect of antipyresis by metamizol, propacetamol or external cooling on metabolism, hemodynamics and inflammatory response.Intensive care medicine · 2004Trial
- An ancient evolutionary origin for IL-1 cytokines.Nature ecology & evolution · 2026Article
- Radiation-Responsive Promoters: Molecular Mechanisms, Screening Strategies, and Translational Applications as Radiation Biomarkers.Current issues in molecular biology · 2026Review
- Immunomodulatory Effects of a Tick Salivary Serpin on Psoriasis-like Inflammation.Life (Basel, Switzerland) · 2026Article
- IL-1 family of cytokines in gastrointestinal and liver disorders.Nature reviews. Gastroenterology & hepatology · 2026Review
- B cells inhibit IL-1 family cytokine production and Mycobacterium tuberculosis growth in human CD14+ cells.ImmunoHorizons · 2025Article
- The protective role of vitamin C against linezolid-induced hepato-renal toxicity in a rat model.Frontiers in pharmacology · 2025Article
- Host Genetic Impact on Infectious Diseases among Different Ethnic Groups.Advanced genetics (Hoboken, N.J.) · 2023Review
- Understanding Ocular Surface Inflammation in Tears Before and After Autologous Cultivated Limbal Epithelial Stem Cell Transplantation.Ophthalmology and therapy · 2023Article
- Humoral Innate Immunity and Acute-Phase Proteins.The New England journal of medicine · 2023Review
- Differential gene expression response of synovial fibroblasts from temporomandibular joints and knee joints to dynamic tensile stress.Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie · 2022Article
- The Effects of 21-Day General Rehabilitation after Hip or Knee Surgical Implantation on Plasma Levels of Selected Interleukins, VEGF, TNF-α, PDGF-BB, and Eotaxin-1.Biomolecules · 2022Article
- Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Pattern of change of C-reactive protein levels and its clinical implication in patients with acute poisoning.SAGE open medicine · 2022Article
- Serum Levels of IL-1 RA Increase with Obesity and Type 2 Diabetes in Relation to Adipose Tissue Dysfunction and are Reduced After Bariatric Surgery in Parallel to Adiposity.Journal of inflammation research · 2022Article
- Article
- Distinct Effects of Interleukin-1β Inhibition upon Cytokine Profile in Patients with Adult-Onset Still's Disease and Active Articular Manifestation Responding to Canakinumab.Journal of clinical medicine · 2021Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Interleukin 1 receptor antagonist (IL-1Ra) levels are elevated in the blood of patients with a variety of infectious, immune, or traumatic conditions. To examine whether IL1Ra is produced by liver cells with characteristics resembling an acute-phase protein, human primary hepatocytes isolated from liver biopsies and HepG2 hepatoma cells were stimulated with IL-1beta, IL-6, and TNFalpha. IL-1Ra was present in the supernatants of both cells, with production significantly enhanced by IL-1beta, and by the combination of IL-1beta and IL-6. The term IL-1Ra refers to two different proteins encoded by the same gene, but generated by alternative splicing of two different first exons. One isoform is secreted (17-kD sIL-1Ra), and the other isoform remains in the cytoplasm (18-kD icIL-1Ra). By Western blot analysis, the supernatants of human hepatoma (HepG2) cells contained only sIL-1Ra, whereas the lysates contained a novel smaller molecular mass isoform of 16 kD. RT-PCR and ribonuclease protection assay with RNA from HepG2 cells showed that only sIL-1Ra mRNA was expressed, and confirmed the inducing effect of IL-1beta and IL-6. Transfection studies were performed using constructs containing the promoters of either sIL-1Ra or icIL-1Ra coupled to the luciferase reporter gene. The sIL-1Ra promoter was active in HepG2 cells stimulated by IL-1beta and/or IL-6, whereas the icIL-1Ra promoter was inactive. Mutation of binding sites for transcription factors NF-kappaB and/or C/EBP within the proximal sIL-1Ra promoter led to significant decreases in response to IL-1beta and IL-6 in comparison to the wild-type promoter. Electromobility gel shift assays confirmed the presence of NF-kappaB and C/EBP binding sites within the sIL-1Ra promoter, and indicated a significant increase in the binding activities of nuclear proteins from HepG2 cells treated with IL-1beta and IL-6. In summary, sIL-1Ra, but not icIL-1Ra, is produced by hepatocytes, and is regulated by proinflammatory cytokines as an acute-phase protein. In addition, NF-kappaB and C/EBP family members are likely to play important roles in the full expression of IL-1Ra by hepatocytes during inflammatory conditions.
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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.