IL1B (interleukin 1, beta)

2008-05-01   Sandra Giraldo , Jesus Sanchez , Quentin Felty , Deodutta Roy 

Department of Environmental, Occupational Health, Robert Stempel School of Public Health, Florida International University, Miami, FL 33199, USA





IL-1beta is located on Chromosome 2 at location 113,303,808-113,310,827. It is located in the middle of IL-1a and IL1-RN between 40 and 110kb from IL-1a. The pro IL-1β gene is composed of seven exons with a primary transcription product length of 7,008 nucleotides.


The gene spans a region of 7.5 kb and the coding part is divided into seven exons.


Transcript length: 1,498 bps; Translation length: 269 residues.



269 amino acids.


IL-1 proteins are considered endogenous pyrogens since they are involved in inflammatory responses and also have been observed to foment prostaglandin and collagenase release from synovial cells. Additionally, IL-1 is responsible for the induction of IL-2 release, B-cell maturation/proliferation, and fibroblast growth factor activity, that stimulates thymocyte proliferation.


IL-1beta shares sequence homology with IL-1a and IL1-RN. IL-1beta and IL-1a have an amino acid homology between them of approximately 25% .

Implicated in

Entity name
Gastric Cancer
Interleukin-1 beta overexpression is associated with the increased risk of both hypochlorhydria induced by H. pylori and gastric cancer (El-Omar et al., 2000). Enhancement of IL-1beta production was determined to be caused by polymorphisms in the interleukin-1 gene cluster. The pro-inflammatory properties of the IL-1 beta cytokine could explain the association with gastric cancer, also considering it is an important inhibitor of acid secretion.
Entity name
Growth of estrogen-dependent tumors
In the pathogenesis of estrogen-dependent cancers, particularly, breast and ovary, the role of IL-1β is implicated in protumorigenic insults, cell proliferation, angiogenesis and cell adhesion. It appears that it is the concentration of the peptide interleukin-1 beta which determines its stimulatory or inhibitory paracrine and/or autocrine signals that regulate the growth of estrogen-dependent tumors. The IL-1β over expressing stable MCF7 cell secreting high level of IL-1β peptides shows inhibition of cell growth compared to nontransfected cells, and elevated level of p53 protein is detected in these cells (Roy et al., 2006). Stably IL-1beta transfected cells secreting moderate level of IL-1β peptides stimulate the clonal expansion of MCF7 cells. Different cellular signaling may operate in response to varying levels of IL-1β leading to genotoxic damage, cell apoptosis or cell growth .
Entity name
Il-1 beta has also been found to stimulate the local production of chemotactic factors for polymorphonuclear leukocytes (PMNs) in tumors; PMNs may play an important role in the inhibition of tumor growth.
On the other hand, other studies have found IL-1 beta to promote tumor growth. According to Vidal-Vanaclocha et al. (2000), IL-1 beta along with tumor necrosis factor-alpha (TNF-alpha), up-regulate the expression of vascular cell adhesion molecule-1 ( VCAM-1 ) on hepatic sinusoidal endothelium (HSE) in vivo which promotes cancer cell adhesion and liver metastases.
Entity name
Cardiovascular Risk, Cardiovascular Diseases
Increased Cardiovascular Risk, Cardiovascular Diseases
SNPs in the interleukin-1beta gene has been reported to be associated with lower expression of basal CRP, a heritable acute-phase plasma protein, in healthy individuals. Elevated basal CRP has been associated with increased cardiovascular risk.
Additionally, an inflammatory cascade involving TNF, IL-1 beta and IL-6 has been suggested to play an important role in the pathogenesis of common postoperative problems associated with cardiac surgery involving a cardiopulmonary bypass. Increased levels of IL-6 release were associated with higher serum levels of TNF-a and IL-1β after surgery, in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).
Entity name
Liver surgery
Changes in tumor necrosis factor-a and interleukin-1 beta production following liver surgery.
For cirrhotic patients undergoing liver surgery, changes of IL-1B and tumor necrosis factor-a levels are observed, suggesting that these two genes play an important role in the pathogenesis of postoperative liver failures. Important tissue injury and/or endotoxin, organ failures could develop and progress after stimulation of cytokine production in monocytes by factors such as insufficient blood supply (ischemia).
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IL-1 beta gene might be an important neuroregulator of responses to inflammatory stressors in the central nervous system considering that overexpression of the IL-1 beta gene has been found in the CNS during systemic inflammation. IL-1a and IL-1b induction in the hypothalamus may regulate neuroendocrine functions during infection and inflammation. Wong et al (1997) propose that actions of brain IL-1 beta during systemic inflammation are an indicator of limited gene expression of cytokines in the brain to counteract IL-1 bioactivity.
Entity name
Rheumatoid Arthritis, Osteoarthritis
IL-1 Beta activity has been linked to a TNF-alpha/cAMP pathway involved in rheumatoid arthritis. Synergistic up-regulation in IL-1 beta synthesis by TNF-alpha/cAMP has been proposed to play a role in the permanent IL-1 beta levels continuously present in chronically inflamed joints. IL-1 beta production is regulated by the TNF-alpha/cAMP pathway at the transcription level requiring a cAMP response element located between -2762 and -2755 bp in the upstream regulatory sequence of IL-1 beta.
Entity name
Periodontal Disease
The severity of periodontal disease could be evaluated through IL-1 beta activity. Liu et al. (1996) identified IL-1beta as playing a pivotal role in the pathogenic mechanism of periodontal tissue destruction. According to the authors, clinical parameters such as gingival index (GI), probing depth (PD) and GCF flow were significantly correlated with gingival crevicular fluid (GCF) and tissue IL-1beta activity. Moreover, the degree of inflammation within periodontal disease tissue could be measured IL-1beta activity in GCF or diseased tissues based on the classification of clinical parameters.
An additional study corroborated above mentioned finding of IL-1 beta levels as a biomarker of periodontal disease. Elevated salivary levels of MMP-8 or IL-1beta or both combined, were found to significantly increase the risk of periodontal disease. Salivary levels of MMP-8 and IL-1beta could serve as biomarkers of periodontitis.
Entity name
Erosive hand osteoarthritis (OA)
There is a significant association between the genomic region containing the IL1B 5810 SNP and erosive hand OA in a group of US Caucasoid population (Stern et al., 2003). The IL1B 5810 AA genotype was significantly associated with the erosive hand OA subgroup (relative risk 3.8, p=0.007). The same genotype association was found significant between erosive and non-erosive hand OA subjects (relative risk 4.01, p=0.008). The IL1B 5810A allele occurs most frequently on haplotypes with the SNP alleles IL1B 1423C, IL1B 1903T, IL1B 5887C, and IL1A (-)889C.


Pubmed IDLast YearTitleAuthors
34906541986Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene.Clark BD et al
107467282000Interleukin-1 polymorphisms associated with increased risk of gastric cancer.El-Omar EM et al
87772751996Relationships between clinical parameters, Interleukin 1B and histopathologic findings of gingival tissue in periodontitis patients.Liu CM et al
76085611995A cyclic adenosine 3',5'-monophosphate signal is required for the induction of IL-1 beta by TNF-alpha in human monocytes.Lorenz JJ et al
165704652006Salivary biomarkers of existing periodontal disease: a cross-sectional study.Miller CS et al
19665511990In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1 beta. II. Mechanism of inhibition: the role of polymorphonuclear leukocytes.Neville ME et al
81882711994A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes.Nicklin MJ et al
183737212008Quantification of the genetic component of basal C-reactive protein expression in SLE nuclear families.Rhodes B et al
114724292001Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass.Roth-Isigkeit A et al
161467802006Levels of IL-1 beta control stimulatory/inhibitory growth of cancer cells.Roy D et al
89085431996Changes in tumor necrosis factor-a and interleukin-1 beta production following liver surgery on cirrhotic patients.Sato T et al
128014792003Association of erosive hand osteoarthritis with a single nucleotide polymorphism on the gene encoding interleukin-1 beta.Stern AG et al
106391482000IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1.Vidal-Vanaclocha F et al
89901901997Interleukin (IL) 1beta, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: pathophysiological implications.Wong ML et al

Other Information

Locus ID:

NCBI: 3553
MIM: 147720
HGNC: 5992
Ensembl: ENSG00000125538


dbSNP: 3553
ClinVar: 3553
TCGA: ENSG00000125538


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
Cytokine-cytokine receptor interactionKEGGko04060
Toll-like receptor signaling pathwayKEGGko04620
Hematopoietic cell lineageKEGGko04640
Type I diabetes mellitusKEGGko04940
Alzheimer's diseaseKEGGko05010
Graft-versus-host diseaseKEGGko05332
MAPK signaling pathwayKEGGhsa04010
Cytokine-cytokine receptor interactionKEGGhsa04060
Toll-like receptor signaling pathwayKEGGhsa04620
Hematopoietic cell lineageKEGGhsa04640
Type I diabetes mellitusKEGGhsa04940
Alzheimer's diseaseKEGGhsa05010
Graft-versus-host diseaseKEGGhsa05332
Prion diseasesKEGGko05020
Prion diseasesKEGGhsa05020
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Cytosolic DNA-sensing pathwayKEGGko04623
Cytosolic DNA-sensing pathwayKEGGhsa04623
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
African trypanosomiasisKEGGko05143
African trypanosomiasisKEGGhsa05143
Rheumatoid arthritisKEGGko05323
Rheumatoid arthritisKEGGhsa05323
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Salmonella infectionKEGGko05132
Salmonella infectionKEGGhsa05132
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
NF-kappa B signaling pathwayKEGGhsa04064
NF-kappa B signaling pathwayKEGGko04064
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Inflammatory bowel disease (IBD)KEGGhsa05321
Inflammatory bowel disease (IBD)KEGGko05321
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Inflammatory mediator regulation of TRP channelsKEGGhsa04750
Inflammatory mediator regulation of TRP channelsKEGGko04750
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
C-type lectin receptors (CLRs)REACTOMER-HSA-5621481
CLEC7A (Dectin-1) signalingREACTOMER-HSA-5607764
CLEC7A/inflammasome pathwayREACTOMER-HSA-5660668
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-1 processingREACTOMER-HSA-448706
Interleukin-1 signalingREACTOMER-HSA-446652
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Antifolate resistanceKEGGko01523
Antifolate resistanceKEGGhsa01523
Th17 cell differentiationKEGGko04659
Th17 cell differentiationKEGGhsa04659
Interleukin-4 and 13 signalingREACTOMER-HSA-6785807
Interleukin-10 signalingREACTOMER-HSA-6783783
IL-17 signaling pathwayKEGGko04657
Fluid shear stress and atherosclerosisKEGGko05418
IL-17 signaling pathwayKEGGhsa04657
Fluid shear stress and atherosclerosisKEGGhsa05418


Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD27498158
PA164713366Tumor necrosis factor alpha (TNF-alpha) inhibitorsChemicalClinicalAnnotationassociatedPD24776844, 28696418
PA166048740Helicobacter InfectionsDiseaseClinicalAnnotationassociatedPD14638340, 16815316, 21054464
PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD27498158
PA443750Colitis, UlcerativeDiseaseClinicalAnnotationassociatedPD24776844
PA443815Crohn DiseaseDiseaseClinicalAnnotationassociatedPD22960943
PA445172Osteitis DeformansDiseaseClinicalAnnotationassociatedPD16257277
PA445210Pain, PostoperativeDiseaseClinicalAnnotationassociatedPD27649267
PA446116Inflammatory Bowel DiseasesDiseaseClinicalAnnotationassociatedPD24776844
PA449548etidronic acidChemicalClinicalAnnotationassociatedPD16257277
PA450180lansoprazoleChemicalClinicalAnnotationassociatedPD14638340, 16815316, 21054464
PA450704omeprazoleChemicalClinicalAnnotationassociatedPD14638340, 16815316, 21054464
PA451216rabeprazoleChemicalClinicalAnnotationassociatedPD14638340, 16815316, 21054464


Pubmed IDYearTitleCitations
121914862002The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.1466
237029782013Activation and regulation of the inflammasomes.736
191885312009Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.670
170360482006Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor.495
185839792008Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database.395
126065242003Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.338
276696502016Mechanism and Regulation of NLRP3 Inflammasome Activation.330
122351172002Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets.313
224662872012Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β.294
191040812009Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages.258


Sandra Giraldo ; Jesus Sanchez ; Quentin Felty ; Deodutta Roy

IL1B (interleukin 1, beta)

Atlas Genet Cytogenet Oncol Haematol. 2008-05-01

Online version: