| Note | |
| Entity | Gastric Cancer |
| Note | 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 | Growth of estrogen-dependent tumors |
| Oncogenesis | 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 | Tumorigenesis |
| Oncogenesis | Il-1 beta has also been found to stimulate the local production of chemotactic factors for polymorphonuclear leukocytes (PMN's) in tumors; PMN's 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 | Cardiovascular Risk, Cardiovascular Diseases |
| Note | Increased Cardiovascular Risk, Cardiovascular Diseases |
| Prognosis | 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 | Liver surgery |
| Note | Changes in tumor necrosis factor-a and interleukin-1 beta production following liver surgery. |
| Oncogenesis | 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). |
| | |
| Entity | Inflammation |
| Prognosis | 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 | Rheumatoid Arthritis, Osteoarthritis |
| Prognosis | 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 | Periodontal Disease |
| Prognosis | 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 | Erosive hand osteoarthritis (OA) |
| Note | 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. |
| | |
| Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene. |
| Clark BD, Collins KL, Gandy MS, Webb AC, Auron PE. |
| Nucleic Acids Res. 1986 Oct 24;14(20):7897-914. |
| PMID 3490654 |
| |
| Interleukin-1 polymorphisms associated with increased risk of gastric cancer. |
| El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF Jr, Rabkin CS. |
| Nature. 2000 Mar 23;404(6776):398-402. Nature 2001 Jul 5;412(6842):99. |
| PMID 10746728 |
| |
| Relationships between clinical parameters, Interleukin 1B and histopathologic findings of gingival tissue in periodontitis patients. |
| Liu CM, Hou LT, Wong MY, Rossomando EF. |
| Cytokine. 1996 Feb;8(2):161-7. |
| PMID 8777275 |
| |
| A cyclic adenosine 3',5'-monophosphate signal is required for the induction of IL-1 beta by TNF-alpha in human monocytes. |
| Lorenz JJ, Furdon PJ, Taylor JD, Verghese MW, Chandra G, Kost TA, Haneline SA, Roner LA, Gray JG. |
| J Immunol. 1995 Jul 15;155(2):836-44. |
| PMID 7608561 |
| |
| Salivary biomarkers of existing periodontal disease: a cross-sectional study. |
| Miller CS, King CP Jr, Langub MC, Kryscio RJ, Thomas MV. |
| J Am Dent Assoc. 2006 Mar;137(3):322-9. |
| PMID 16570465 |
| |
| In vivo inhibition of tumor growth of B16 melanoma by recombinant interleukin 1 beta. II. Mechanism of inhibition: the role of polymorphonuclear leukocytes. |
| Neville ME, Pezzella KM, Schmidt K, Galbraith W, Ackerman N. |
| Cytokine. 1990 Nov;2(6):456-63. |
| PMID 1966551 |
| |
| A physical map of the region encompassing the human interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist genes. |
| Nicklin MJ, Weith A, Duff GW. |
| Genomics. 1994 Jan 15;19(2):382-4. |
| PMID 8188271 |
| |
| Quantification of the Genetic Component of Basal C-Reactive Protein Expression in SLE Nuclear Families. |
| Rhodes B, Meek J, Whittaker JC, Vyse TJ. |
| Ann Hum Genet. 2008 Mar 27. [Epub ahead of print] |
| PMID 18373721 |
| |
| Inter-individual differences in cytokine release in patients undergoing cardiac surgery with cardiopulmonary bypass. |
| Roth-Isigkeit A, Hasselbach L, Ocklitz E, Brückner S, Ros A, Gehring H, Schmucker P, Rink L, Seyfarth M. |
| Clin Exp Immunol. 2001 Jul;125(1):80-8. |
| PMID 11472429 |
| |
| Levels of IL-1 beta control stimulatory/inhibitory growth of cancer cells. |
| Roy D, Sarkar S, Felty Q. |
| Front Biosci. 2006 Jan 1;11:889-98. |
| PMID 16146780 |
| |
| Changes in tumor necrosis factor-a and interleukin-1 beta production following liver surgery on cirrhotic patients. |
| Sato T, Asanuma Y, Masaki Y, Sato Y, Hatakeyama Y, Kusano T, Koyama K. |
| Hepatogastroenterology. 1996 Sep-Oct;43(11):1148-53. |
| PMID 8908543 |
| |
| Association of erosive hand osteoarthritis with a single nucleotide polymorphism on the gene encoding interleukin-1 beta. |
| Stern AG, de Carvalho MR, Buck GA, Adler RA, Rao TP, Disler D, Moxley G; I-NODAL Network. |
| Osteoarthritis Cartilage. 2003 Jun;11(6):394-402. |
| PMID 12801479 |
| |
| IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. |
| Vidal-Vanaclocha F, Fantuzzi G, Mendoza L, Fuentes AM, Anasagasti MJ, Martin J, Carrascal T, Walsh P, Reznikov LL, Kim SH, Novick D, Rubinstein M, Dinarello CA. |
| Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):734-9. |
| PMID 10639148 |
| |
| Interleukin (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, Bongiorno PB, Rettori V, McCann SM, Licinio J. |
| Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):227-32. |
| PMID 8990190 |
| |
