Affinage

Showing IL1RN — IRAP is a alias.

IL1RN

Interleukin-1 receptor antagonist protein · UniProt P18510

Length
177 aa
Mass
20.1 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IL1RN encodes interleukin-1 receptor antagonist (IL-1Ra), a competitive inhibitor of IL-1 signaling whose loss removes the brake on IL-1-driven inflammation (PMID:19494219, PMID:22127713). Homozygous deletion of the IL1RN locus causes the severe autoinflammatory disease DIRA, in which patient mononuclear cells overproduce inflammatory cytokines and symptoms are completely reversed by recombinant IL-1Ra (anakinra) (PMID:19494219); an in-frame deletion that abolishes IL-1 receptor binding reproduces the cytokine oversecretion phenotype, establishing that receptor occupancy is the basis of IL-1Ra's anti-inflammatory function (PMID:22127713). In Il1rn-deficient mice, unrestrained IL-1 signaling directly activates keratinocytes to make TNF and chemokines, producing T-cell-independent psoriasis-like dermatitis that requires TNF from skin-resident cells (PMID:20610641), and delays resolution of acute lung inflammation by acting upstream of an IL-17A/G-CSF axis driven by gamma-delta T cells (PMID:22592923). Beyond antagonizing secreted IL-1, an intracellular isoform (icIL-1RA1) restrains the senescence-associated secretory phenotype in keratinocytes (PMID:33526711), and IL-1Ra additionally promotes osteoblast differentiation through an integrin-beta3/beta-catenin interaction (PMID:33493267) and supports endothelial cell replicative capacity (PMID:12764021). IL1RN expression is set transcriptionally by GATA-1 at the rs4251961 promoter SNP (PMID:21248262) and by ELF4 (PMID:38022496), and post-transcriptionally by miR-125a-5p and miR-122-5p targeting its 3'UTR (PMID:38875998, PMID:34594415); functional coding and regulatory variants that alter mRNA and plasma IL-1Ra abundance modulate susceptibility to ARDS, septic shock, and pulmonary fibrosis (PMID:23449693, PMID:25089931, PMID:22322675).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1993 Medium

    Establishing where IL1RN sits in the genome placed it within the interleukin-1 gene family, framing it as a paralog-derived modulator of IL-1 biology.

    Evidence Cell hybrid panel, family linkage, and FISH with a YAC probe localizing IL1RN to chromosome 2q14

    PMID:1386337 PMID:8432529

    Open questions at the time
    • Genomic mapping does not define protein function or mechanism
    • Does not address how the gene is regulated or which cells express it
  2. 2011 High

    Human loss-of-function genetics resolved the question of whether IL-1Ra is physiologically required to restrain IL-1, showing that its absence or inability to bind receptor causes unchecked IL-1 signaling and severe autoinflammation.

    Evidence Homozygous IL1RN deletion in DIRA patients with ex vivo cytokine assays and anakinra rescue, plus an in-frame deletion yielding a receptor-binding-null mutant tested in vitro and in patient cells

    PMID:19494219 PMID:22127713

    Open questions at the time
    • Defines requirement but not the structural basis of receptor antagonism
    • Does not address tissue-specific or intracellular roles of IL-1Ra
  3. 2012 High

    Mouse knockout studies defined the cellular pathways through which IL-1Ra loss drives organ-specific inflammation, mapping IL-1 to keratinocyte TNF in skin and to an IL-17A/G-CSF axis in lung resolution.

    Evidence Il1rn-/- mice with cytokine knockout crosses, adoptive transfer, bone marrow transplantation, aerosolized LPS, and IL-17A antibody blockade

    PMID:20610641 PMID:22592923

    Open questions at the time
    • Downstream effectors mapped in mouse may differ across human tissues
    • Does not establish the molecular step at which IL-1Ra sets each threshold
  4. 2014 High

    Genetic and human-challenge studies tied specific IL1RN variants to plasma IL-1Ra abundance and clinical outcome, showing that variation acting at the mRNA level modulates susceptibility to ARDS, septic shock, and fibrosis.

    Evidence Multi-cohort association studies with paired plasma IL-1Ra ELISA, allelic imbalance by RNA-seq of adipose tissue, human LPS endotoxin challenge, and genotype-stratified mRNA analysis

    PMID:22322675 PMID:23449693 PMID:25089931

    Open questions at the time
    • Variant-to-expression mechanism not resolved for synonymous rs315952 at the molecular level
    • Effect sizes and replication vary by clinical condition
  5. 2021 Medium

    Functional studies expanded IL-1Ra beyond receptor antagonism, identifying intracellular SASP suppression, an osteogenic integrin-beta3/beta-catenin role, and endothelial proliferative support.

    Evidence CRISPR knockdown of icIL-1RA1 in keratinocytes with cytokine/senescence readouts, gain/loss-of-function in osteoblast lines with ITGB3 interaction, and genotype-stratified endothelial cultures with IL-1Ra supplementation

    PMID:12764021 PMID:33493267 PMID:33526711

    Open questions at the time
    • Single-lab findings for each non-canonical role
    • Mechanistic link between intracellular IL-1Ra and SASP not fully defined
    • ITGB3 interaction not structurally characterized
  6. 2023 Medium

    Regulatory studies established how IL1RN expression is controlled, identifying transcriptional activators (GATA-1, ELF4) and microRNA repressors (miR-125a-5p, miR-122-5p) that tune IL-1Ra levels and inflammatory tone.

    Evidence Promoter-reporter assays with GATA-1, ChIP and luciferase for ELF4, and dual-luciferase 3'UTR validation for miR-125a-5p and miR-122-5p with in vivo disease models

    PMID:21248262 PMID:34594415 PMID:38022496 PMID:38875998

    Open questions at the time
    • Regulators identified in separate disease contexts, not integrated
    • Relative contribution of each regulator to physiological IL-1Ra levels unknown
  7. 2023 Medium

    Cancer studies positioned IL1RN/IL-1Ra as a modulator of the tumor immune microenvironment and tumor cell proliferation.

    Evidence Methionine-deprivation and knockdown in glioma with cell cycle analysis, and KRAS-mutant iCCA mouse models with isoform overexpression, anakinra, and anti-PD-1 combination

    PMID:30978442 PMID:37486241

    Open questions at the time
    • Tumor-context roles are single-study and tumor-type specific
    • Mechanism linking IL1RN to glioma cell cycle arrest not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the canonical secreted antagonist, the intracellular isoforms, and the integrin/beta-catenin signaling activity are mechanistically partitioned within a single tissue remains unresolved.
  • No unified model reconciling receptor antagonism with intracellular and pro-differentiation roles
  • Structural basis of IL-1Ra receptor binding versus ITGB3 binding not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0048018 receptor ligand activity 1
Localization
GO:0005576 extracellular region 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2
Partners
IL1R1ITGB3

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 IL1RN gene maps to chromosome 2q14-q21, in the same region as IL-1alpha and IL-1beta loci, consistent with an early gene duplication event creating an interleukin-1 gene family. Somatic rodent-human cell hybrid panel analysis and linkage analysis in CEPH families using a length variation polymorphism in intron 2 Genomics Medium 1386337
1993 The human IL1RN gene was localized to chromosome 2q14.2 by fluorescence in situ hybridization using a yeast artificial chromosome containing IL1RN as a probe, near the IL-1alpha, IL-1beta, and IL-1 receptor genes. FISH with YAC probe; Southern blot of human-Chinese hamster cell hybrids Genomics Medium 8432529
2009 Homozygous deletion of the IL1RN locus (175-kb deletion at chromosome 2q13) causes a severe autoinflammatory disease (DIRA) characterized by pustular rash, lytic bone lesions, osteopenia, respiratory insufficiency, and thrombosis; mononuclear cells from the patient produced markedly elevated inflammatory cytokines, and treatment with anakinra (recombinant IL-1Ra) completely resolved symptoms, establishing that absence of IL-1Ra protein causes unchecked IL-1 signaling. Genetic analysis (homozygous deletion identified), ex vivo cytokine production assay of patient mononuclear cells, therapeutic rescue with anakinra The New England journal of medicine High 19494219
2011 A novel homozygous 15-bp in-frame deletion in IL1RN produces a mutant IL-1Ra protein that has no affinity for the IL-1 receptor in vitro, and patient cells stimulated with IL-1alpha or IL-1beta showed oversecretion of proinflammatory cytokines, demonstrating that receptor binding is required for IL-1Ra's anti-inflammatory function. In vitro expression of mutant protein with IL-1 receptor binding assay; stimulation of patient cells with recombinant IL-1alpha/IL-1beta and cytokine measurement Arthritis and rheumatism High 22127713
2010 In Il1rn-/- mice, spontaneous psoriasis-like dermatitis is driven by excess IL-1 signaling that directly activates keratinocytes to produce TNF and chemokines; development of dermatitis requires TNF (completely suppressed in Tnfsf1a-/- mice) but not IL-6 or IL-17, and is T-cell independent (lesions develop in Il1rn-/- SCID mice; adoptive transfer of Il1rn-/- T cells does not induce dermatitis). Bone marrow transplantation showed that TNF from skin-resident (non-bone marrow-derived) cells is critical. Genetic knockout mice (Il1rn-/-, Tnfsf1a-/-, Il6-/-, IL-17-deficient crosses); adoptive transfer experiments into SCID mice; bone marrow transplantation; cytokine/chemokine measurement at inflammation site Journal of immunology High 20610641
2012 In Il1rn-/- mice exposed to aerosolized LPS, resolution of lung inflammation is delayed relative to wild-type, with increased BAL neutrophils, elevated IL-17A expression (from gamma-delta T cells), and elevated G-CSF. Blockade of IL-17A reduced BAL neutrophil counts and lung G-CSF expression in Il1rn-/- mice, placing IL-1Ra upstream of the IL-17A/G-CSF axis in resolution of acute lung inflammation. Knockout mouse model (Il1rn-/-) with aerosolized LPS; BAL cell counts and protein measurement; cytokine/RNA profiling; IL-17A monoclonal antibody blockade American journal of respiratory cell and molecular biology High 22592923
2011 The IL1RN promoter SNP rs4251961 (C allele) is associated with increased plasma IL-1Ra concentrations during invasive pneumococcal disease. Functional reporter assays in HEK293T cells showed that the C allele promoter construct has ~9-fold increased activity versus ~6-fold for the T allele in the presence of GATA-1, identifying GATA-1 as a differential transcriptional regulator of IL1RN expression at this locus. Promoter-reporter (luciferase) transfection assay in HEK293T cells with and without GATA-1 overexpression; plasma IL-1Ra measurement in 299 children with invasive pneumococcal disease; validation in HIV-infected adult cohort Journal of immunology Medium 21248262
2013 The IL1RN coding variant rs315952C is associated with decreased risk of ARDS in three independent populations; carriers of rs315952C have higher plasma IL-1Ra levels, establishing that this synonymous variant functionally influences IL1Ra protein levels and thereby modulates ARDS susceptibility. Multi-stage genetic association study (three critically ill cohorts, n=3065 total); ELISA for plasma IL-1Ra protein levels stratified by genotype American journal of respiratory and critical care medicine High 23449693
2014 The IL1RN synonymous coding variant rs315952C is preferentially transcribed (allelic imbalance demonstrated by RNA sequencing of adipose tissue), leading to higher evoked plasma IL-1Ra after LPS challenge and improved survival in septic shock, establishing that this variant acts at the level of mRNA expression to modulate IL-1Ra protein levels and downstream clinical outcomes. RNA sequencing of adipose tissue for allelic imbalance; human LPS endotoxin challenge model (n=294 volunteers) with plasma IL-1Ra ELISA; genetic association study for survival in the VASST septic shock cohort American journal of respiratory and critical care medicine High 25089931
2012 The IL1RN VNTR*2 haploblock is associated with IPF susceptibility, and the IL1RN SNP rs2637988 significantly influences IL-1Ra mRNA expression levels (carriers of the minor GG genotype have lower mRNA), suggesting that reduced IL-1Ra expression predisposes to pulmonary fibrosis. Meta-analysis of five case-control studies; IL1RN mRNA expression analysis correlated with genotype in patient samples Immunogenetics Medium 22322675
2021 Intracellular IL-1RA type 1 (icIL-1RA1, a product of IL1RN) is progressively lost during oral carcinogenesis; CRISPR/Cas9-mediated knockdown of icIL-1RA1 in normal and dysplastic oral keratinocytes caused increased IL-6 and IL-8 secretion and accelerated senescence, establishing icIL-1RA1 as a regulator of the senescence-associated secretory phenotype (SASP). CRISPR/Cas9 knockdown in primary keratinocytes; IL-6/IL-8 ELISA; senescence assay; ex vivo tissue expression analysis Journal of cell science Medium 33526711
2021 IL1RN promotes osteoblast differentiation by interacting with integrin beta3 (ITGB3) to activate beta-catenin signaling; silencing IL1RN attenuated osteogenic differentiation while overexpression increased alkaline phosphatase, osterix, and osteocalcin expression in MC3T3-E1 and C3H10T1/2 cells. IL1RN knockdown and overexpression in osteoblast cell lines; co-interaction assay with ITGB3; osteogenic staining; Western blot for osteogenic markers and beta-catenin pathway components Acta biochimica et biophysica Sinica Medium 33493267
2019 IL1RN mediates the suppressive effect of methionine deprivation on glioma cell proliferation; methionine deprivation or IL1RN knockdown induced glioma cell cycle arrest both in vitro and in vivo. Methionine deprivation experiments in glioma cell lines; IL1RN knockdown; cell cycle analysis; in vivo tumor model Cancer letters Medium 30978442
2023 In KRAS-mutant intrahepatic cholangiocarcinoma, alternative splicing upregulates IL1RN-201/203 isoforms as a negative feedback mechanism; both IL1RN-201/203 upregulation and anakinra treatment altered neutrophil recruitment/phenotypes and activated intratumoral GZMB+ CD8+ T cells, and synergized with anti-PD-1 therapy in KRAS-mutant iCCA mouse models. Multiomics analysis of patient samples; in vivo KRAS-mutant iCCA mouse models with IL1RN isoform overexpression and anakinra treatment; flow cytometry for immune cell phenotyping; combination with anti-PD-1 Cancer discovery Medium 37486241
2024 Exosomal miR-125a-5p from cigarette smoke-exposed bronchial epithelial cells is taken up by macrophages and targets IL1RN (confirmed by luciferase reporter assay), reducing IL-1Ra expression and promoting M1 macrophage polarization via the MyD88/NF-κB pathway. Luciferase reporter assay for miR-125a-5p targeting of IL1RN 3'UTR; PKH26-labeled exosome uptake; co-culture of epithelial cells and macrophages; miR-125a-5p mimic/inhibitor transfection; in vivo COPD mouse model with miR-125a-5p inhibitor International immunopharmacology Medium 38875998
2021 miR-122-5p directly targets IL1RN (confirmed by TargetScan prediction and dual luciferase reporter assay); miR-122-5p mimics decreased cell viability and promoted apoptosis/inflammation in LPS-treated A549 cells, and these effects were reversed by IL1RN siRNA knockdown, establishing IL1RN as a functional target of miR-122-5p in LPS-induced lung injury. Dual luciferase reporter gene assay; miR-122-5p mimic/inhibitor transfection; IL1RN siRNA; LPS-induced ALI cell model; ELISA for TNF-alpha, IL-1beta, IL-6 Experimental and therapeutic medicine Medium 34594415
2023 The transcription factor ELF4 activates IL1RN transcription; dual-luciferase and ChIP assays in BMDMs and intestinal epithelial cells demonstrated ELF4 binding to the IL1RN promoter and increased IL1RN promoter activity. ELF4-driven IL1RN upregulation suppressed inflammatory TH17 cell activity and induced macrophage M2 polarization to alleviate experimental colitis. Dual-luciferase reporter assay; ChIP assay; ELF4 overexpression in vivo (LPS-induced colitis mouse model); flow cytometry for macrophage polarization and TH17 cells; ELISA Frontiers in immunology Medium 38022496
2003 The IL-1RN*2/*2 genotype is associated with decreased endothelial cell (EC) cumulative population doublings and reduced proliferation at later passage, with increased senescent ECs. Addition of exogenous IL-1Ra (1 ng/mL) increased proliferation of IL-1RN*2/*2 ECs, suggesting that IL-1Ra promotes EC replicative capacity. Ex vivo EC culture from human donors stratified by IL-1RN genotype; Ki67 proliferation assay; cumulative population doubling counts; exogenous IL-1Ra supplementation Circulation research Medium 12764021

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scandinavian journal of immunology 479 9519856
2009 An autoinflammatory disease due to homozygous deletion of the IL1RN locus. The New England journal of medicine 299 19494219
2004 Genetic polymorphisms of interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor {alpha} and risk of gastric cancer in a Chinese population. Carcinogenesis 183 15579481
1992 The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci. Genomics 147 1386337
1996 Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus. Human genetics 131 8786086
2005 Role of the polymorphic IL-1B, IL-1RN and TNF-A genes in distal gastric cancer in Mexico. International journal of cancer 104 15540224
2004 Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: association with knee osteoarthritis. Genes and immunity 104 15190266
2022 Single-cell RNA sequencing identifies an Il1rn+/Trem1+ macrophage subpopulation as a cellular target for mitigating the progression of thoracic aortic aneurysm and dissection. Cell discovery 86 35132073
2006 IL-1RN gene polymorphism is associated with peri-implantitis. Clinical oral implants research 82 16907768
2011 A novel mutation of IL1RN in the deficiency of interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil. Arthritis and rheumatism 74 22127713
2002 Smoking and polymorphisms of the interleukin-1 gene cluster (IL-1alpha, IL-1beta, and IL-1RN) in patients with periodontal disease. Journal of periodontology 73 11846196
2013 Activation of human mesenchymal stem cells impacts their therapeutic abilities in lung injury by increasing interleukin (IL)-10 and IL-1RN levels. Stem cells translational medicine 71 24089414
2008 Polymorphisms of the IL1-receptor antagonist gene (IL1RN) are associated with multiple markers of systemic inflammation. Arteriosclerosis, thrombosis, and vascular biology 70 18451331
2006 IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy. Pharmacogenomics 68 16886894
2004 IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis. Gastroenterology 61 15236174
2011 Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis. Clinical and experimental immunology 60 22059992
2005 IL-1RN and IL-1B gene polymorphisms and cerebral hemorrhagic events after traumatic brain injury. Neurology 60 16217062
2002 Helicobacter pylori virulence genes and host IL-1RN and IL-1beta genes interplay in favouring the development of peptic ulcer and intestinal metaplasia. Cytokine 60 12161099
2001 The polymorphic IL-1B and IL-1RN genes in the aetiopathogenesis of peptic ulcer. Clinical and experimental immunology 59 11531943
1993 The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region. Genomics 59 8432529
2005 Interleukin 1B gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in Helicobacter pylori-negative gastric cancer of intestinal and diffuse histotype. Annals of oncology : official journal of the European Society for Medical Oncology 58 15851404
2013 IL1RN coding variant is associated with lower risk of acute respiratory distress syndrome and increased plasma IL-1 receptor antagonist. American journal of respiratory and critical care medicine 56 23449693
2005 IL1RN polymorphic gene and cagA-positive status independently increase the risk of noncardia gastric carcinoma. International journal of cancer 56 15704154
2012 IL1RN genetic variations and risk of IPF: a meta-analysis and mRNA expression study. Immunogenetics 53 22322675
2003 Polymorphisms of IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, and IFN-gamma genes in the Korean population. Human immunology 51 14522096
2011 Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis. Journal of clinical gastroenterology 49 20975573
2011 The first reported case of compound heterozygous IL1RN mutations causing deficiency of the interleukin-1 receptor antagonist. Arthritis and rheumatism 49 21792839
2005 NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's disease. Inflammatory bowel diseases 47 15803022
2021 Early Treatment and IL1RN Single-Nucleotide Polymorphisms Affect Response to Anakinra in Systemic Juvenile Idiopathic Arthritis. Arthritis & rheumatology (Hoboken, N.J.) 46 33615724
2018 IL1RN Variation Influences Both Disease Susceptibility and Response to Recombinant Human Interleukin-1 Receptor Antagonist Therapy in Systemic Juvenile Idiopathic Arthritis. Arthritis & rheumatology (Hoboken, N.J.) 44 29609200
1999 Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus erythematosus. Lupus 44 10192503
2003 High-throughput single-nucleotide polymorphism analysis of the IL1RN locus in patients with ankylosing spondylitis by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Arthritis and rheumatism 43 12847695
2014 A functional synonymous coding variant in the IL1RN gene is associated with survival in septic shock. American journal of respiratory and critical care medicine 41 25089931
2005 Polymorphisms of TNFalpha, IL1beta, and IL1RN genes in chronic obstructive pulmonary disease. Biochemical and biophysical research communications 41 15766560
2019 Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease. Annals of the rheumatic diseases 39 31852669
2009 Association between IL4 (-590), ACE (I)/(D), CCR5 (Delta32), CTLA4 (+49) and IL1-RN (VNTR in intron 2) gene polymorphisms and vitiligo. European journal of dermatology : EJD 38 19129082
2011 Polymorphisms in interleukin-1B (IL-1B) and interleukin 1 receptor antagonist (IL-1RN) genes associate with gastric cancer risk in the Chinese population. Digestive diseases and sciences 37 21243433
2010 TNF, but not IL-6 and IL-17, is crucial for the development of T cell-independent psoriasis-like dermatitis in Il1rn-/- mice. Journal of immunology (Baltimore, Md. : 1950) 37 20610641
2006 Role of the NFKB1 -94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes. Inflammatory bowel diseases 37 16804398
2009 Genotypic and functional roles of IL-1B and IL-1RN on the risk of gastroesophageal reflux disease: the presence of IL-1B-511*T/IL-1RN*1 (T1) haplotype may protect against the disease. The American journal of gastroenterology 36 19603010
2005 Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer. Cancer letters 36 16019127
2012 Association of NOS2 and potential effect of VEGF, IL6, CCL2 and IL1RN polymorphisms and haplotypes on susceptibility to GCA--a simultaneous study of 130 potentially functional SNPs in 14 candidate genes. Rheumatology (Oxford, England) 35 22258388
2009 Analysis of the association of IL1B (C+3954T) and IL1RN (intron 2) polymorphisms with dental implant loss in a Brazilian population. Clinical oral implants research 35 19191798
2005 Genetic polymorphisms of interleukin-1 beta (IL-1B) and IL-1 receptor antagonist (IL-1RN) and breast cancer risk in Korean women. Breast cancer research and treatment 35 16319982
2015 Interleukin-1 receptor antagonist (IL1RN) is associated with suppression of early carcinogenic events in human oral malignancies. International journal of oncology 34 25738940
2023 An Inflammatory Checkpoint Generated by IL1RN Splicing Offers Therapeutic Opportunity for KRAS-Mutant Intrahepatic Cholangiocarcinoma. Cancer discovery 32 37486241
2013 Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus. Investigative ophthalmology & visual science 32 23462747
2011 The IL1RN promoter rs4251961 correlates with IL-1 receptor antagonist concentrations in human infection and is differentially regulated by GATA-1. Journal of immunology (Baltimore, Md. : 1950) 32 21248262
2017 Deficiency of Interleukin-1 Receptor Antagonist (DIRA): Report of the First Indian Patient and a Novel Deletion Affecting IL1RN. Journal of clinical immunology 31 28503715
2012 IL1 receptor antagonist gene IL1-RN variable number of tandem repeats polymorphism and cancer risk: a literature review and meta-analysis. PloS one 30 23049925
2009 Association of genetic variation in serum amyloid-A with cardiovascular disease and interactions with IL6, IL1RN, IL1beta and TNF genes in the Cardiovascular Health Study. Journal of atherosclerosis and thrombosis 30 19729864
2024 Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease. International immunopharmacology 29 38875998
2015 Association study of functional polymorphisms in interleukins and interleukin receptors genes: IL1A, IL1B, IL1RN, IL6, IL6R, IL10, IL10RA and TGFB1 in schizophrenia in Polish population. Schizophrenia research 29 26481614
2010 IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia. British journal of haematology 28 20626741
2003 Interleukin-1 receptor antagonist (IL-1RN) genotype modulates the replicative capacity of human endothelial cells. Circulation research 27 12764021
2001 Absence of a genetic association between IL-1RN and IL-1B gene polymorphisms in ulcerative colitis and Crohn disease in multiple populations from northeast England. Scandinavian journal of gastroenterology 27 11686217
2020 New variant in the IL1RN-gene (DIRA) associated with late-onset, CRMO-like presentation. Rheumatology (Oxford, England) 26 32259833
2008 Association of IL-4 and IL-1RN (receptor antagonist) gene variants and the risk of type 2 diabetes mellitus: a study in the north Indian population. Indian journal of medical sciences 26 18688110
2007 [Association of cytokines genes (ILL, IL1RN, TNF, LTA, IL6, IL8, IL0) polymorphic markers with chronic obstructive pulmonary disease]. Molekuliarnaia biologiia 26 17380888
2007 Potential influence of IL1B haplotype and IL1A-IL1B-IL1RN extended haplotype on hand osteoarthritis risk. Osteoarthritis and cartilage 26 17532232
2006 Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1B gene polymorphisms in Turkish patients with rheumatoid arthritis. Clinical and experimental rheumatology 26 17207379
2002 Linkage and association studies of IL1B and IL1RN gene polymorphisms in preeclampsia. Hypertension in pregnancy 26 12044341
2007 IL1RN VNTR polymorphism in ischemic stroke: analysis in 3 populations. Stroke 25 17332449
2006 Interleukin-1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms and gastric cancer risk in an Omani Arab population. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 25 17235630
2014 Genetic polymorphism of interleukin-1A (IL-1A), IL-1B, and IL-1 receptor antagonist (IL-1RN) and prostate cancer risk. Asian Pacific journal of cancer prevention : APJCP 24 25374200
2012 Distribution of the IL-1RN, IL-6, IL-10, INF-γ, and TNF-α Gene Polymorphisms in the Mexican Population. Genetic testing and molecular biomarkers 24 22971140
2010 Polymorphisms of interleukin 1 gene IL1RN are associated with Tourette syndrome. Pediatric neurology 24 20399384
2014 Stroke, IL-1ra, IL1RN, infection and outcome. Neurocritical care 23 24233813
2009 Combined polymorphism analysis of glutathione S-transferase M1/G1 and interleukin-1B (IL-1B)/interleukin 1-receptor antagonist (IL-1RN) and gastric cancer risk in an Omani Arab Population. Journal of clinical gastroenterology 23 18779738
2009 Breast cancer risk associated with polymorphisms of IL-1RN and IL-4 gene in Indian women. Oncology research 23 19544973
2023 Recombinant Interleukin-1 Receptor Antagonist Is an Effective First-Line Treatment Strategy in New-Onset Systemic Juvenile Idiopathic Arthritis, Irrespective of HLA-DRB1 Background and IL1RN Variants. Arthritis & rheumatology (Hoboken, N.J.) 22 37471469
2019 Helicobacter pylori and Epstein-Barr Virus Infection in Gastric Diseases: Correlation with IL-10 and IL1RN Polymorphism. Journal of oncology 22 31885568
2008 Role of host interleukin 1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN) polymorphisms in clinical outcomes in Helicobacter pylori-positive Turkish patients with dyspepsia. Journal of gastroenterology 22 18807132
2008 Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic conditions: Association of IL-1RN*2/2 genotype with polymyalgia rheumatica. Human immunology 22 19026700
2023 DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis. Journal of proteomics 21 37657716
2009 Association between IL-1B and IL-1RN gene polymorphisms and Chagas' disease development susceptibility. Immunological investigations 21 19811434
2014 Association between the IL1B, IL1RN polymorphisms and COPD risk: a meta-analysis. Scientific reports 20 25174605
2012 Delayed resolution of lung inflammation in Il-1rn-/- mice reflects elevated IL-17A/granulocyte colony-stimulating factor expression. American journal of respiratory cell and molecular biology 20 22592923
2003 Interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms are not associated with tubal pathology and Chlamydia trachomatis-related tubal factor subfertility. Human reproduction (Oxford, England) 20 14585879
2016 Interaction of IL1B and IL1RN polymorphisms, smoking habit, gender, and ethnicity with aggressive and chronic periodontitis susceptibility. Contemporary clinical dentistry 19 27630500
2012 Interleukin 1 receptor antagonist (IL1RN) genetic variations condition post-orthodontic external root resorption in endodontically-treated teeth. Histology and histopathology 19 23212299
2010 Influence of IL-1RN intron 2 variable number of tandem repeats (VNTR) polymorphism on the age at onset of neuropsychiatric symptoms in Wilson's disease. The International journal of neuroscience 19 20942594
2005 IL1RN polymorphism and cagA-positive Helicobacter pylori strains increase the risk of duodenal ulcer in children. Pediatric research 19 16183821
2004 Replication test for association of the IL-1 receptor antagonist gene, IL1RN, with attention-deficit/hyperactivity disorder. Neuropsychobiology 19 15365221
2021 IL1RN promotes osteoblastic differentiation via interacting with ITGB3 in osteoporosis. Acta biochimica et biophysica Sinica 18 33493267
2021 The role of icIL-1RA in keratinocyte senescence and development of the senescence-associated secretory phenotype. Journal of cell science 18 33526711
2019 Association of ENAM, TUFT1, MMP13, IL1B, IL10 and IL1RN gene polymorphism and dental caries susceptibility in Chinese children. The Journal of international medical research 18 30803280
2017 Common variants in IL-1RN, IL-1β and TNF-α and the risk of ovarian cancer: a case control study. Central-European journal of immunology 18 28860932
2014 Genetic polymorphisms of surfactant protein D rs2243639, Interleukin (IL)-1β rs16944 and IL-1RN rs2234663 in chronic obstructive pulmonary disease, healthy smokers, and non-smokers. Molecular diagnosis & therapy 18 24504887
2009 Interleukin-1 receptor antagonist gene (IL1RN) polymorphism possibly associated to severity of rheumatic carditis in a Brazilian cohort. Cytokine 18 19822442
2017 A link between osteomyelitis and IL1RN and IL1B polymorphisms-a study in patients from Northeast Brazil. Acta orthopaedica 17 28682145
2012 IL-1RN VNTR polymorphism and genetic susceptibility to cervical cancer in Portugal. Molecular biology reports 17 23053980
2011 IL1B -511(G>A) and IL1RN (VNTR) allelic polymorphisms and susceptibility to knee osteoarthritis in Croatian population. Rheumatology international 17 21523343
2010 Variable number of tandem repeat polymorphisms of the interleukin-1 receptor antagonist gene IL-1RN: a novel association with the athlete status. BMC medical genetics 17 20175886
2008 Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study. Human immunology 17 18396210
2018 A novel mutation of interleukin-1 receptor antagonist (IL1RN) in a DIRA patient from Turkey: Diagnosis and treatment. The Turkish journal of pediatrics 16 30968643
2023 The transcription factor ELF4 alleviates inflammatory bowel disease by activating IL1RN transcription, suppressing inflammatory TH17 cell activity, and inducing macrophage M2 polarization. Frontiers in immunology 15 38022496
2021 miR-122-5p downregulation attenuates lipopolysaccharide-induced acute lung injury by targeting IL1RN. Experimental and therapeutic medicine 15 34594415
2019 IL1RN mediates the suppressive effect of methionine deprivation on glioma proliferation. Cancer letters 15 30978442
2008 Interleukin-1 receptor antagonist gene (IL-1RN) polymorphism is a predictive factor of clinical pregnancy after IVF. Human reproduction (Oxford, England) 15 18332090

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