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Gene Review

Il1rn  -  interleukin 1 receptor antagonist

Mus musculus

Synonyms: F630041P17Rik, IL-1RN, IL-1ra, IL1 inhibitor, IRAP, ...
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Disease relevance of Il1rn

  • RESULTS: We show that the expression of Il1rn and the gene encoding the inhibitory type II IL-1 receptor was upregulated in diet-induced obesity [1].
  • Using a mouse model relevant to ITP, we confirm an increase in mouse serum levels of IL-1Ra after exposure to IVIg, yet a recombinant IL-1Ra did not ameliorate thrombocytopenia [2].
  • Thus, local IL-1ra gene therapy may represent a therapeutic alternative for the inhibition of immune-mediated demyelination of the CNS.Gene Therapy (2007) 14, 93-98. doi:10.1038/; published online 24 August 2006 [3].
  • IL-1ra tended to decrease bone resorption at the proximal tibia; however, it had no effect on quantitatively measured bone parameters [4].
  • This study examines the effects of an IL-6-producing murine multiple myeloma cell line on trabecular and cortical mouse bone, and evaluates the efficacy of interleukin-1 receptor antagonist (IL-1ra) in mitigating bone destruction [4].

Psychiatry related information on Il1rn


High impact information on Il1rn


Chemical compound and disease context of Il1rn


Biological context of Il1rn

  • METHODS: We assessed the expression of genes related to IL-1 signalling in the WAT of mice fed a high-fat diet, as well as the effect of Il1rn (the gene for IL-1Ra) deletion and treatment with IL-1Ra on glucose homeostasis in rodents [1].
  • The IL-1ra gene (Il1rn) maps near the allergen-induced bronchial hyper-responsiveness-1 locus, Abhr1, which we previously mapped to murine chromosome 2 using A/J (asthma susceptible) and C3H/HeJ (asthma resistant) mice [13].
  • When these IL1-ra overexpressing transgenic mice on the LDLR knockout background were fed a high-cholesterol/high-fat diet containing cholate, however, a statistically significant 40% decrease in lesion area was observed compared to LDLR knockout mice lacking the transgene [14].
  • Studies have suggested that IVIg may function through the regulation of cytokines, including interleukin-1 receptor antagonist (IL-1Ra), an inhibitor of phagocytosis [2].
  • RESULTS: All IL-1Ra(-/-) mice receiving BMT showed marked improvement in arthritis within 3 weeks, as well as successful induction of mixed chimerism [15].

Anatomical context of Il1rn

  • The blood insulin:glucose ratio was significantly lower in Il1rn ( -/- )animals, which is compatible with an increased sensitivity to insulin, reinforced by the fact that the insulin content and pancreatic islet morphology of Il1rn ( -/- ) animals were normal [1].
  • These data demonstrate that in selected models of murine atherosclerosis, chronic IL-1ra depletion or overexpression has potentially important effects on lipoprotein metabolism and foam-cell lesion development [14].
  • Immunoregulatory effects of allogeneic mixed chimerism induced by nonmyeloablative bone marrow transplantation on chronic inflammatory arthritis and autoimmunity in interleukin-1 receptor antagonist-deficient mice [15].
  • METHODS: IL-1Ra(-/-) mice (H-2K(d)) were treated with antibody to asialoganglioside G(M1) (anti-natural killer cell), total body irradiation (500 cGy), and T cell-depleted, nonmyeloablative BMT derived from C57BL/6 mice (H-2K(b)) [15].
  • Amelioration of EAE course was associated with a reduced number of macrophages infiltrating the CNS and in a decreased level of proinflammatory cytokine mRNA in the CNS, suggesting an inhibitory activity of IL-1ra on effector cell recruitment, as antigen-specific peripheral T-cell activation and T-cell recruitment to the CNS is unaffected [3].

Associations of Il1rn with chemical compounds

  • We evaluated the role of Il1rn in our mouse model by comparing its genomic sequence between A/J and C3H/HeJ mice as well as assessing strain-specific RNA and protein production in response to allergen [13].
  • In summary, IL-1ra tended to increase plasma lipoprotein levels and, when fed a cholate-containing diet, decrease foam-cell lesion size [14].
  • IL-1ra knockout C57BL/6J mice fed a cholesterol/cholate diet for 3 mo had a 3-fold decrease in non-high-density lipoprotein cholesterol and a trend toward increased foam-cell lesion area compared to wild-type littermate controls [14].
  • This was abolished by IL-1ra (20 ng/ml), an antagonist of the IL-1 receptor, and by SB203580 (5 muM), a p38 MAPK inhibitor [16].
  • Myeloma animals were further assigned to three unique groups: MPC-11 only; MPC-11 treated with hyaluronic acid (HA); and MPC-11 + IL-1ra/HA (100 mg/kg) [4].

Physical interactions of Il1rn


Regulatory relationships of Il1rn


Other interactions of Il1rn


Analytical, diagnostic and therapeutic context of Il1rn

  • The goal of this study was to examine lipoprotein levels and early atherosclerosis in chronic animal models of altered IL-1 physiology by using mice with deficient or excess IL-1 receptor antagonist (IL-1ra) [14].
  • IL-1ra gene therapy is effective preventively, delaying EAE onset by almost 1 week (22.4+/-1.4 days post-immunization vs 15.9+/-2.1 days in control mice; P=0.0229 log-rank test), and decreasing disease severity [3].
  • Since IL-1 synthesis has been suggested to occur locally in brain tissue, we investigated the expression of IL-1 (alpha and beta) and IL-1 receptor antagonist (IL-1ra) mRNAs in various structures of the central nervous system, as well as in the spleen, following intraperitoneal injection of LPS (100 micrograms/mouse) [23].
  • Effects of therapy with interleukin-1 receptor antagonist on pulmonary cytokine expression following hemorrhage and resuscitation [24].
  • Inhibition of IL-1 function by the in vivo administration of IL-1 receptor antagonist (IL-1ra) reduces the immunosuppression and mortality of GVHD without impairing the engraftment of hematopoietic stem cells [25].


  1. Interleukin-1 receptor antagonist is upregulated during diet-induced obesity and regulates insulin sensitivity in rodents. Somm, E., Cettour-Rose, P., Asensio, C., Charollais, A., Klein, M., Theander-Carrillo, C., Juge-Aubry, C.E., Dayer, J.M., Nicklin, M.J., Meda, P., Rohner-Jeanrenaud, F., Meier, C.A. Diabetologia (2006) [Pubmed]
  2. A role for IL-1 receptor antagonist or other cytokines in the acute therapeutic effects of IVIg? Crow, A.R., Song, S., Semple, J.W., Freedman, J., Lazarus, A.H. Blood (2007) [Pubmed]
  3. HSV-1-mediated IL-1 receptor antagonist gene therapy ameliorates MOG(35-55)-induced experimental autoimmune encephalomyelitis in C57BL/6 mice. Furlan, R., Bergami, A., Brambilla, E., Butti, E., De Simoni, M.G., Campagnoli, M., Marconi, P., Comi, G., Martino, G. Gene Ther. (2007) [Pubmed]
  4. Effect of MPC-11 myeloma and MPC-11 + IL-1 receptor antagonist treatment on mouse bone properties. Ferguson, V.L., Simske, S.J., Ayers, R.A., Bateman, T.A., Wang, H.T., Bendele, A., Rich, B., Collins, D., Scherrer, J., Sennello, R., Colagiovanni, D.B. Bone (2002) [Pubmed]
  5. The role of cytokines in the behavioral responses to endotoxin and influenza virus infection in mice: effects of acute and chronic administration of the interleukin-1-receptor antagonist (IL-1ra). Swiergiel, A.H., Smagin, G.N., Johnson, L.J., Dunn, A.J. Brain Res. (1997) [Pubmed]
  6. Production of mice deficient in genes for interleukin (IL)-1alpha, IL-1beta, IL-1alpha/beta, and IL-1 receptor antagonist shows that IL-1beta is crucial in turpentine-induced fever development and glucocorticoid secretion. Horai, R., Asano, M., Sudo, K., Kanuka, H., Suzuki, M., Nishihara, M., Takahashi, M., Iwakura, Y. J. Exp. Med. (1998) [Pubmed]
  7. Differential roles of IL-1 and TNF-alpha on graft-versus-host disease and graft versus leukemia. Hill, G.R., Teshima, T., Gerbitz, A., Pan, L., Cooke, K.R., Brinson, Y.S., Crawford, J.M., Ferrara, J.L. J. Clin. Invest. (1999) [Pubmed]
  8. Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice. Kitazawa, R., Kimble, R.B., Vannice, J.L., Kung, V.T., Pacifici, R. J. Clin. Invest. (1994) [Pubmed]
  9. Histopathology of acetaminophen-induced liver changes: role of interleukin 1 alpha and tumor necrosis factor alpha. Blazka, M.E., Elwell, M.R., Holladay, S.D., Wilson, R.E., Luster, M.I. Toxicologic pathology. (1996) [Pubmed]
  10. Inhibition by interleukin 1 receptor antagonist of in vivo activities of interleukin 1 in mice. Mengozzi, M., Bertini, R., Sironi, M., Ghezzi, P. Lymphokine Cytokine Res. (1991) [Pubmed]
  11. Interleukin-1 receptor antagonist modulates the progression of a spontaneously occurring IgA nephropathy in mice. Chen, A., Sheu, L.F., Chou, W.Y., Tsai, S.C., Chang, D.M., Liang, S.C., Lin, F.G., Lee, W.H. Am. J. Kidney Dis. (1997) [Pubmed]
  12. Interleukin-1 receptor antagonist prevents low dose streptozotocin induced diabetes in mice. Sandberg, J.O., Andersson, A., Eizirik, D.L., Sandler, S. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  13. IL-1 Receptor antagonist as a positional candidate gene in a murine model of allergic asthma. Ramadas, R.A., Li, X., Shubitowski, D.M., Samineni, S., Wills-Karp, M., Ewart, S.L. Immunogenetics (2006) [Pubmed]
  14. Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size. Devlin, C.M., Kuriakose, G., Hirsch, E., Tabas, I. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  15. Immunoregulatory effects of allogeneic mixed chimerism induced by nonmyeloablative bone marrow transplantation on chronic inflammatory arthritis and autoimmunity in interleukin-1 receptor antagonist-deficient mice. Cho, S.G., Min, S.Y., Park, M.J., Lee, K.W., Cho, Y.G., Cho, M.L., Chang, H.S., Park, S.H., Lee, J.W., Min, W.S., Kim, C.C., Kim, H.Y. Arthritis Rheum. (2006) [Pubmed]
  16. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Zhu, C.B., Blakely, R.D., Hewlett, W.A. Neuropsychopharmacology (2006) [Pubmed]
  17. Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice. Elhage, R., Maret, A., Pieraggi, M.T., Thiers, J.C., Arnal, J.F., Bayard, F. Circulation (1998) [Pubmed]
  18. The roles of IL-1, IL-6, and TNFalpha in the feeding responses to endotoxin and influenza virus infection in mice. Swiergiel, A.H., Dunn, A.J. Brain Behav. Immun. (1999) [Pubmed]
  19. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. Li, Y., Liu, L., Barger, S.W., Griffin, W.S. J. Neurosci. (2003) [Pubmed]
  20. Leptin actions on food intake and body temperature are mediated by IL-1. Luheshi, G.N., Gardner, J.D., Rushforth, D.A., Loudon, A.S., Rothwell, N.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  21. Soluble interleukin-1 receptor accessory protein ameliorates collagen-induced arthritis by a different mode of action from that of interleukin-1 receptor antagonist. Smeets, R.L., Joosten, L.A., Arntz, O.J., Bennink, M.B., Takahashi, N., Carlsen, H., Martin, M.U., van den Berg, W.B., van de Loo, F.A. Arthritis Rheum. (2005) [Pubmed]
  22. Interleukin-1 receptor antagonist decreases severity of experimental acute pancreatitis. Norman, J., Franz, M., Messina, J., Riker, A., Fabri, P.J., Rosemurgy, A.S., Gower, W.R. Surgery (1995) [Pubmed]
  23. Expression of interleukin 1 alpha, interleukin 1 beta and interleukin 1 receptor antagonist mRNA in mouse brain: regulation by bacterial lipopolysaccharide (LPS) treatment. Gabellec, M.M., Griffais, R., Fillion, G., Haour, F. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  24. Effects of therapy with interleukin-1 receptor antagonist on pulmonary cytokine expression following hemorrhage and resuscitation. Abraham, E., Allbee, J. Lymphokine Cytokine Res. (1994) [Pubmed]
  25. Inhibition of interleukin-1 by an interleukin-1 receptor antagonist prevents graft-versus-host disease. McCarthy, P.L., Abhyankar, S., Neben, S., Newman, G., Sieff, C., Thompson, R.C., Burakoff, S.J., Ferrara, J.L. Blood (1991) [Pubmed]
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