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Gene Review

IL1RN  -  interleukin 1 receptor antagonist

Homo sapiens

Synonyms: DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3, ...
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Disease relevance of IL1RN

  • Whether the IL1RN polymorphism makes a direct functional contribution to the pathogenesis of Graves' disease or is acting as a marker for a linked gene is being investigated [1].
  • Individuals carrying 2 or more of the risk-associated alleles (IL1B-31C, IL1RN *2 and IL10-592C) were at increased risk for intestinal-type gastric cancer, compared to those with 0 or 1 risk-associated allele [2].
  • Combining the available data on the IL1RN VNTR suggests that any effect of this gene on susceptibility to multiple sclerosis, or its progression is, at best, small [3].
  • A positive but not significant association was found between the allele 2 of the IL1RN and the presence of multifocal atrophic gastritis [4].
  • Polymorphisms of TNFalpha, IL1beta, and IL1RN genes in chronic obstructive pulmonary disease [5].

Psychiatry related information on IL1RN


High impact information on IL1RN


Chemical compound and disease context of IL1RN

  • However, delaying the initial IL-1ra treatment 3 hours after the induction of colitis (total 6 doses) was effective in reducing inflammatory index (by 60%), MPO activity (by 79%), PGE2 (by 62%), and LTB4 (by 72%) whereas colonic IL-1 alpha levels were unchanged compared with vehicle-treated animals [12].
  • The effects of human recombinant interleukin-1 receptor antagonist (IL-1ra) on inflammation, tissue damage, and production of inflammatory mediators in rabbit formalin-immune complex colitis were examined [12].
  • To address the cellular source of IL-1 and IL-1ra mRNA in the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with BAL cells (95% PMNs) obtained 6 hours after IT injection of LPS [13].
  • The activity of interleukin-1 (IL-1), a powerful stimulant of osteoclastic bone resorption, is increased in estrogen-deficient states with increased production of IL-1 and inhibition of the IL-1 receptor antagonist (IL-1ra) [14].
  • The purpose of this was to study evaluate the effects of interleukin-1 (IL-1) inhibition by human recombinant IL-1 receptor antagonist (IL-1ra) on plasma prostaglandin, leukotriene, and cytokine levels in sepsis syndrome [15].

Biological context of IL1RN

  • Lack of linkage of IL1RN genotypes with ankylosing spondylitis susceptibility [16].
  • Enzyme-linked immunosorbent assays showed decreased baseline plasma levels of IL-1ra in patients with type 2 diabetes, which may in part explain the role of the IL1RN VNTR in these patients [17].
  • Two polymorphisms within IL1B (3953C>T and -511C>T) and one within IL1RN (the variable-number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA [18].
  • Three SNPs located in the 3' region of the IL1RN gene (T/C at position 27810 in exon 4, T/C at position 30735 in exon 6, and G/C at position 31017 in exon 6) were examined by high-throughput MassArray MALDI-TOF mass spectrometry [19].
  • Association with specific haplotypes raises the possibility that the primary disease locus is in linkage disequilibrium with a specific combination(s) of markers in the IL1RN gene [19].

Anatomical context of IL1RN


Associations of IL1RN with chemical compounds


Physical interactions of IL1RN


Regulatory relationships of IL1RN


Other interactions of IL1RN

  • IL-1ra production by monocytes, macrophages, and neutrophils may be regulated in a differential fashion with IL-1 beta [38].
  • Moreover, IL-1ra mRNA levels were maximal after 6 hr of exposure to LPS but peaked within the first 3 hr in the presence of IL-4 [34].
  • In the G-CSF-pretreated subjects endotoxin-induced surges in rectal temperature and in the plasma levels of TNF-alpha plasma levels were about 50% increased, and surges in the plasma levels of both sTNF-Rs and IL-1ra were about twice as high as in the control group [39].
  • Serum IL-6 levels were significantly higher in SPA patients than in PM/DM patients, whereas serum IL-1ra and sTNFR levels were significantly higher in PM/DM than in SPA patients [40].
  • However, IL-1ra had no effect on proliferative responses elicited in LAK cells by IL-2 [41].

Analytical, diagnostic and therapeutic context of IL1RN


  1. Association of Graves' disease with an allele of the interleukin-1 receptor antagonist gene. Blakemore, A.I., Watson, P.F., Weetman, A.P., Duff, G.W. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  2. Gastric cancer risk in a Mexican population: role of Helicobacter pylori CagA positive infection and polymorphisms in interleukin-1 and -10 genes. Sicinschi, L.A., Lopez-Carrillo, L., Camargo, M.C., Correa, P., Sierra, R.A., Henry, R.R., Chen, J., Zabaleta, J., Piazuelo, M.B., Schneider, B.G. Int. J. Cancer (2006) [Pubmed]
  3. Interleukin 1 receptor antagonist (IL-1ra) in multiple sclerosis. Feakes, R., Sawcer, S., Broadley, S., Coraddu, F., Roxburgh, R., Gray, J., Clayton, D., Compston, A. J. Neuroimmunol. (2000) [Pubmed]
  4. Association of interleukin-1beta gene polymorphisms with precancerous gastric lesions in African Americans and Caucasians. Zabaleta, J., Camargo, M.C., Piazuelo, M.B., Fontham, E., Schneider, B.G., Sicinschi, L.A., Ferrante, W., Balart, L., Correa, P., Ochoa, A.C. Am. J. Gastroenterol. (2006) [Pubmed]
  5. Polymorphisms of TNFalpha, IL1beta, and IL1RN genes in chronic obstructive pulmonary disease. Hegab, A.E., Sakamoto, T., Saitoh, W., Nomura, A., Ishii, Y., Morishima, Y., Iizuka, T., Kiwamoto, T., Matsuno, Y., Massoud, H.H., Massoud, H.M., Hassanein, K.M., Sekizawa, K. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  6. Replication test for association of the IL-1 receptor antagonist gene, IL1RN, with attention-deficit/hyperactivity disorder. Misener, V.L., Schachar, R., Ickowicz, A., Malone, M., Roberts, W., Tannock, R., Kennedy, J.L., Pathare, T., Barr, C.L. Neuropsychobiology (2004) [Pubmed]
  7. Decreased levels of intrathecal interleukin 1 receptor antagonist in Alzheimer's disease. Tarkowski, E., Liljeroth, A.M., Nilsson A, n.u.l.l., Minthon, L., Blennow, K. Dementia and geriatric cognitive disorders. (2001) [Pubmed]
  8. Cortisol responses to mild psychological stress are inversely associated with proinflammatory cytokines. Kunz-Ebrecht, S.R., Mohamed-Ali, V., Feldman, P.J., Kirschbaum, C., Steptoe, A. Brain Behav. Immun. (2003) [Pubmed]
  9. Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease. Janszky, I., Lekander, M., Blom, M., Georgiades, A., Ahnve, S. Brain Behav. Immun. (2005) [Pubmed]
  10. Umbilical cord levels of interleukin-1 receptor antagonist and neonatal outcome. Elsmén, E., Ley, D., Cilio, C.M., Hansen-Pupp, I., Hellstrom-Westas, L. Biol. Neonate (2006) [Pubmed]
  11. Interleukin-1 receptor antagonist: role in biology. Arend, W.P., Malyak, M., Guthridge, C.J., Gabay, C. Annu. Rev. Immunol. (1998) [Pubmed]
  12. Recombinant interleukin-1 receptor antagonist blocks the proinflammatory activity of endogenous interleukin-1 in rabbit immune colitis. Cominelli, F., Nast, C.C., Duchini, A., Lee, M. Gastroenterology (1992) [Pubmed]
  13. Endotoxin-induced cytokine gene expression in vivo. IV. Expression of interleukin-1 alpha/beta and interleukin-1 receptor antagonist mRNA during endotoxemia and during endotoxin-initiated local acute inflammation. Ulich, T.R., Guo, K., Yin, S., del Castillo, J., Yi, E.S., Thompson, R.C., Eisenberg, S.P. Am. J. Pathol. (1992) [Pubmed]
  14. Allelic variation at the interleukin-1 receptor antagonist gene is associated with early postmenopausal bone loss at the spine. Keen, R.W., Woodford-Richens, K.L., Lanchbury, J.S., Spector, T.D. Bone (1998) [Pubmed]
  15. Interleukin-1 mediates increased plasma levels of eicosanoids and cytokines in patients with sepsis syndrome. Slotman, G.J., Friedman, B., Brathwaite, C., Mure, A.J., Quinn, J.V., Shapiro, E. Shock (1995) [Pubmed]
  16. Lack of linkage of IL1RN genotypes with ankylosing spondylitis susceptibility. Jin, L., Zhang, G., Akey, J.M., Luo, J., Lee, J., Weisman, M.H., Bruckel, J., Inman, R.D., Stone, M.A., Khan, M.A., Schumacher, H.R., Maksymowych, W.P., Mahowald, M.L., Sawitzke, A.D., Vasey, F.B., Yu, D.T., Reveille, J.D. Arthritis Rheum. (2004) [Pubmed]
  17. Interleukin-1 receptor antagonist genotype is associated with coronary atherosclerosis in patients with type 2 diabetes. Marculescu, R., Endler, G., Schillinger, M., Iordanova, N., Exner, M., Hayden, E., Huber, K., Wagner, O., Mannhalter, C. Diabetes (2002) [Pubmed]
  18. Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis of the hip. Meulenbelt, I., Seymour, A.B., Nieuwland, M., Huizinga, T.W., van Duijn, C.M., Slagboom, P.E. Arthritis Rheum. (2004) [Pubmed]
  19. 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. Maksymowych, W.P., Reeve, J.P., Reveille, J.D., Akey, J.M., Buenviaje, H., O'Brien, L., Peloso, P.M., Thomson, G.T., Jin, L., Russell, A.S. Arthritis Rheum. (2003) [Pubmed]
  20. Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitis. Carter, M.J., Jones, S., Camp, N.J., Cox, A., Mee, J., Warren, B., Duff, G.W., Lobo, A.J., di Giovine, F.S. Genes Immun. (2004) [Pubmed]
  21. Polymorphism in the interleukin-1 gene complex and spontaneous preterm delivery. Genç, M.R., Gerber, S., Nesin, M., Witkin, S.S. Am. J. Obstet. Gynecol. (2002) [Pubmed]
  22. Purification, cloning, expression and biological characterization of an interleukin-1 receptor antagonist protein. Carter, D.B., Deibel, M.R., Dunn, C.J., Tomich, C.S., Laborde, A.L., Slightom, J.L., Berger, A.E., Bienkowski, M.J., Sun, F.F., McEwan, R.N. Nature (1990) [Pubmed]
  23. Inhibition of interleukin 1 (IL-1) binding and bioactivity in vitro and modulation of acute inflammation in vivo by IL-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody. McIntyre, K.W., Stepan, G.J., Kolinsky, K.D., Benjamin, W.R., Plocinski, J.M., Kaffka, K.L., Campen, C.A., Chizzonite, R.A., Kilian, P.L. J. Exp. Med. (1991) [Pubmed]
  24. Tissue interleukin 1 and interleukin-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats. McCall, R.D., Haskill, S., Zimmermann, E.M., Lund, P.K., Thompson, R.C., Sartor, R.B. Gastroenterology (1994) [Pubmed]
  25. Production of interleukin-1 receptor antagonist, inflammatory chemotactic proteins, and prostaglandin E by rheumatoid and osteoarthritic synoviocytes--regulation by IFN-gamma and IL-4. Seitz, M., Loetscher, P., Dewald, B., Towbin, H., Ceska, M., Baggiolini, M. J. Immunol. (1994) [Pubmed]
  26. Unopposed interleukin-1 is necessary for increased plasma cytokine and eicosanoid levels to develop in severe sepsis. Slotman, G.J., Quinn, J.V., Wry, P.C., Brathwaite, C.E., Friedman, B.M. Ann. Surg. (1997) [Pubmed]
  27. Monocytic secretion of interleukin-1 receptor antagonist in normal and osteoporotic women: effects of menopause and estrogen/progesterone therapy. Pacifici, R., Vannice, J.L., Rifas, L., Kimble, R.B. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  28. Serum interleukin 1 receptor antagonist as an independent marker of non-alcoholic steatohepatitis in humans. Pihlajamäki, J., Kuulasmaa, T., Kaminska, D., Simonen, M., Kärjä, V., Grönlund, S., Käkelä, P., Pääkkönen, M., Kainulainen, S., Punnonen, K., Kuusisto, J., Gylling, H., Laakso, M. J. Hepatol. (2011) [Pubmed]
  29. Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: I. IL-1 receptor antagonist inhibits IL-1-induced cytokine synthesis and blocks the binding of IL-1 to its type II receptor on human monocytes. Granowitz, E.V., Clark, B.D., Vannier, E., Callahan, M.V., Dinarello, C.A. Blood (1992) [Pubmed]
  30. Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. Granowitz, E.V., Clark, B.D., Mancilla, J., Dinarello, C.A. J. Biol. Chem. (1991) [Pubmed]
  31. Regulation of interleukin-1ra, interleukin-1 alpha, and interleukin-1 beta production by human alveolar macrophages with phorbol myristate acetate, lipopolysaccharide, and interleukin-4. Galve-de Rochemonteix, B., Nicod, L.P., Chicheportiche, R., Lacraz, S., Baumberger, C., Dayer, J.M. Am. J. Respir. Cell Mol. Biol. (1993) [Pubmed]
  32. Combined treatment of acute EAE in Lewis rats with TNF-binding protein and interleukin-1 receptor antagonist. Wiemann, B., Van, G.Y., Danilenko, D.M., Yan, Q., Matheson, C., Munyakazi, L., Ogenstad, S., Starnes, C.O. Exp. Neurol. (1998) [Pubmed]
  33. IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium. Firestein, G.S., Berger, A.E., Tracey, D.E., Chosay, J.G., Chapman, D.L., Paine, M.M., Yu, C., Zvaifler, N.J. J. Immunol. (1992) [Pubmed]
  34. Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist. Vannier, E., Miller, L.C., Dinarello, C.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  35. Interleukin-1 receptor antagonist protein inhibits interleukin-8 expression in lipopolysaccharide-stimulated human whole blood. DeForge, L.E., Tracey, D.E., Kenney, J.S., Remick, D.G. Am. J. Pathol. (1992) [Pubmed]
  36. X-ray structure of interleukin-1 receptor antagonist at 2.0-A resolution. Vigers, G.P., Caffes, P., Evans, R.J., Thompson, R.C., Eisenberg, S.P., Brandhuber, B.J. J. Biol. Chem. (1994) [Pubmed]
  37. Tumor necrosis factor-alpha induces interleukin-1 alpha and interleukin-1 receptor antagonist production by cultured human keratinocytes. Kutsch, C.L., Norris, D.A., Arend, W.P. J. Invest. Dermatol. (1993) [Pubmed]
  38. Interleukin-1 receptor antagonist. Arend, W.P. Adv. Immunol. (1993) [Pubmed]
  39. Effects of granulocyte colony-stimulating factor on plasma cytokine and cytokine receptor levels and on the in vivo host response to endotoxin in healthy men. Pollmächer, T., Korth, C., Mullington, J., Schreiber, W., Sauer, J., Vedder, H., Galanos, C., Holsboer, F. Blood (1996) [Pubmed]
  40. Elevated serum levels of interleukin-1 receptor antagonist in polymyositis/dermatomyositis. A biologic marker of disease activity with a possible role in the lack of acute-phase protein response. Gabay, C., Gay-Croisier, F., Roux-Lombard, P., Meyer, O., Maineti, C., Guerne, P.A., Vischer, T., Dayer, J.M. Arthritis Rheum. (1994) [Pubmed]
  41. Regulation of lymphokine-activated killer cell induction by human recombinant IL-1 receptor antagonist. Obligate paracrine pathway of IL-1 during lymphokine-activated killer cell induction. Fujiwara, T., Grimm, E.A. J. Immunol. (1992) [Pubmed]
  42. Genetic control of IL-1beta bioactivity through differential regulation of the IL-1 receptor antagonist. Vamvakopoulos, J., Green, C., Metcalfe, S. Eur. J. Immunol. (2002) [Pubmed]
  43. Identification of genes predominantly expressed in human macrophages. Svensson, P.A., Hägg, D.A., Jernås, M., Englund, M.C., Hulten, L.M., Ohlsson, B.G., Hulthe, J., Wiklund, O., Carlsson, B., Fagerberg, B., Carlsson, L.M. Atherosclerosis (2004) [Pubmed]
  44. The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region. Patterson, D., Jones, C., Hart, I., Bleskan, J., Berger, R., Geyer, D., Eisenberg, S.P., Smith, M.F., Arend, W.P. Genomics (1993) [Pubmed]
  45. Interleukin 1 beta and tumor necrosis factor levels in stored platelet concentrates and the association with gene polymorphisms. Addas-Carvalho, M., Origa, A.F., Saad, S.T. Transfusion (2004) [Pubmed]
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