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Gene Review

Il4  -  interleukin 4

Rattus norvegicus

Synonyms: B-cell IGG differentiation factor, B-cell growth factor 1, B-cell stimulatory factor 1, BSF-1, IL-4, ...
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Disease relevance of Il4


High impact information on Il4


Chemical compound and disease context of Il4


Biological context of Il4


Anatomical context of Il4

  • Sensitized skin from IL-4(-/-) mice displayed normal thickening of the skin layers but had a drastic reduction in eosinophils and a significant increase in infiltrating T cells [1].
  • Adenoviruses encoding IL-4 (AdIL-4) or IL-10 (AdIL-10) were administered to rats through the portal vein and the anti-adenovirus immune response was studied [17].
  • T-helper subset 2 (Th2) lymphocytes produce interleukin 4 (IL-4) and IL-10, which exert anti-inflammatory actions on monocytes and macrophages [18].
  • Absorption experiments demonstrated that when BCGF activity was absorbed out by large, activated human B cells, astrocyte-stimulatory activity was also depleted [19].
  • Rat astrocytes were able to partially absorb out both BCGF and astrocyte-stimulatory activity [19].

Associations of Il4 with chemical compounds

  • CONCLUSION: In rat AIA, IL-4 reduces synovial tissue vascularization via angiostatic effects, mediates inhibition of angiogenesis via an association with altered pro- and antiangiogenic cytokines, and may inhibit VEGF-mediated angiogenesis and exert its angiostatic role in part via alphavbeta3 integrin [2].
  • Furthermore, the treatment with pioglitazone decreased the expression levels of proinflamatory cytokine (TNF alpha and IL-1beta) genes and Th1 cytokine (IFN-gamma) genes, and increased the expression levels of Th2 cytokine (IL-4) gene [20].
  • Over several experiments, with or without IL-4 and/or IFN-gamma, serotonin release correlated inversely with nitrite production [21].
  • Purified rat splenic CD8+ T cells were cultured for 6 days with PMA, ionomycin and IL-2 with or without IL-4 or anti-IFN-gamma and restimulated with PMA and ionomycin [22].
  • Reciprocal effects of interleukin-4 and interferon-gamma on immunoglobulin E-mediated mast cell degranulation: a role for nitric oxide but not peroxynitrite or cyclic guanosine monophosphate [21].

Regulatory relationships of Il4

  • In situ hybridization showed that cells expressing IL-4 and -5 mRNA were increased in the airways of the lungs of BN rats after OA challenge (P < 0.05) and that cells expressing mRNA for IFN-gamma and IL-2 were higher in SD than in BN rats after antigen challenge (P < 0.05) [23].
  • Results from PCR showed that prior to antigen challenge, BN rats expressed in their lungs mRNA for IL-4 and -5 and SD rats expressed very little mRNA for IL-5 only [23].
  • Both IFN-gamma and IL-4 enhanced MCP-1 mRNA levels but with different kinetics [24].
  • B cells from Lewis rats showed a similar IL-4-induced enhancement of RT1.B expression (2.5-fold), whereas, in contrast, RT1.D expression was unmodified [25].
  • IL-10 was more effective than IL-4 in suppressing iNOS expression and, interestingly, IL-10 conferred protection against oligodendroglial death evoked by LPS/IFN-gamma [26].

Other interactions of Il4

  • In contrast, CD45RC- CD8+ T cells from hepatic allografts pretreated with PVG.r1 blood expressed IL-4, IL-10, and IFN-lambda, but not IL-2 [27].
  • Our results showed that the mean values for IL-4 and IL-5 mRNA were increased significantly in sensitized rats compared with control rats [28].
  • Both CD4+ and CD8+ T cells are activated in response to allergen challenge in the sensitized rat and express Thelper2 cytokines (IL-4, IL-5 and IL-13) [29].
  • In contrast, the brain of S. pneumoniae-inoculated rats showed lower levels of IL-1beta, IL-6 and TNF-alpha, but higher levels of TNF-beta and detectable mRNA expression of IL-4 when compared with Hib-inoculated rats [30].
  • The serum level of IL-1 beta and IL-4 showed no significant change [31].

Analytical, diagnostic and therapeutic context of Il4


  1. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. Spergel, J.M., Mizoguchi, E., Oettgen, H., Bhan, A.K., Geha, R.S. J. Clin. Invest. (1999) [Pubmed]
  2. Inhibition of angiogenesis by interleukin-4 gene therapy in rat adjuvant-induced arthritis. Haas, C.S., Amin, M.A., Allen, B.B., Ruth, J.H., Haines, G.K., Woods, J.M., Koch, A.E. Arthritis Rheum. (2006) [Pubmed]
  3. Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells. Issazadeh, S., Mustafa, M., Ljungdahl, A., Höjeberg, B., Dagerlind, A., Elde, R., Olsson, T. J. Neurosci. Res. (1995) [Pubmed]
  4. Induction of interleukin-4 and interleukin-5 expression in mast cells is inhibited by glucocorticoids. Sewell, W.A., Scurr, L.L., Orphanides, H., Kinder, S., Ludowyke, R.I. Clin. Diagn. Lab. Immunol. (1998) [Pubmed]
  5. Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC- cells and CD4(+)CD8(-) thymocytes. Seddon, B., Mason, D. J. Exp. Med. (1999) [Pubmed]
  6. The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC class II-restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production. McMenamin, C., Holt, P.G. J. Exp. Med. (1993) [Pubmed]
  7. Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain. Khoury, S.J., Hancock, W.W., Weiner, H.L. J. Exp. Med. (1992) [Pubmed]
  8. Glucocorticoids induce the expression of CD8 alpha chains on concanavalin A-activated rat CD4+ T cells: induction is inhibited by rat recombinant interleukin 4. Ramirez, F., McKnight, A.J., Silva, A., Mason, D. J. Exp. Med. (1992) [Pubmed]
  9. Effect of allergen-specific immunotherapy on interleukin-4, interleukin-5 and interferon-gamma mRNA expression in the nasal mucosa of rats with allergic rhinitis. El-Naggar, M.M., Ukai, K., Takeuchi, K., Sakakura, Y. Scand. J. Immunol. (1998) [Pubmed]
  10. Antifibrotic effect of interferon gamma in silicosis model of rat. Chen, Y., Chen, J., Dong, J., Liu, W. Toxicol. Lett. (2005) [Pubmed]
  11. Protective effect of Rolipram in experimental autoimmune neuritis: protection is associated with down-regulation of IFN-gamma and inflammatory chemokines as well as up-regulation of IL-4 in peripheral nervous system. Abbas, N., Zou, L.P., Pelidou, S.H., Winblad, B., Zhu, J. Autoimmunity (2000) [Pubmed]
  12. Regulation of found in inflammatory zone 1 expression in bleomycin-induced lung fibrosis: role of IL-4/IL-13 and mediation via STAT-6. Liu, T., Jin, H., Ullenbruch, M., Hu, B., Hashimoto, N., Moore, B., McKenzie, A., Lukacs, N.W., Phan, S.H. J. Immunol. (2004) [Pubmed]
  13. Dexamethasone inhibits the anti-tumor effect of interleukin 4 on rat experimental gliomas. Benedetti, S., Pirola, B., Poliani, P.L., Cajola, L., Pollo, B., Bagnati, R., Magrassi, L., Tunici, P., Finocchiaro, G. Gene Ther. (2003) [Pubmed]
  14. Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats. David, A., Chétritt, J., Guillot, C., Tesson, L., Heslan, J.M., Cuturi, M.C., Soulillou, J.P., Anegon, I. Gene Ther. (2000) [Pubmed]
  15. Th1/Th2 cytokine gene expression after mercuric chloride in susceptible and resistant rat strains. Gillespie, K.M., Saoudi, A., Kuhn, J., Whittle, C.J., Druet, P., Bellon, B., Mathieson, P.W. Eur. J. Immunol. (1996) [Pubmed]
  16. N-3 fatty acids modulate Th1 and Th2 dichotomy in diabetic pregnancy and macrosomia. Khan, N.A., Yessoufou, A., Kim, M., Hichami, A. J. Autoimmun. (2006) [Pubmed]
  17. Anti-adenovirus immune responses in rats are enhanced by interleukin 4 but not interleukin 10 produced by recombinant adenovirus. David, A., Coupel-Clauce, H., Chetritt, J., Tesson, L., Cassard, A., Charreau, B., Soulillou, J.P., Anegon, I. Hum. Gene Ther. (1998) [Pubmed]
  18. Anti-inflammatory lymphokine mRNA expression in antibody-induced glomerulonephritis. Lakkis, F.G., Baddoura, F.K., Cruet, E.N., Parekh, K.R., Fukunaga, M., Munger, K.A. Kidney Int. (1996) [Pubmed]
  19. Human B cell growth factor enhances proliferation and glial fibrillary acidic protein gene expression in rat astrocytes. Benveniste, E.N., Whitaker, J.N., Gibbs, D.A., Sparacio, S.M., Butler, J.L. Int. Immunol. (1989) [Pubmed]
  20. Pioglitazone, a peroxisome proliferator-activated receptor gamma activator, ameliorates experimental autoimmune myocarditis by modulating Th1/Th2 balance. Hasegawa, H., Takano, H., Zou, Y., Qin, Y., Hizukuri, K., Odaka, K., Toyozaki, T., Komuro, I. J. Mol. Cell. Cardiol. (2005) [Pubmed]
  21. Reciprocal effects of interleukin-4 and interferon-gamma on immunoglobulin E-mediated mast cell degranulation: a role for nitric oxide but not peroxynitrite or cyclic guanosine monophosphate. Deschoolmeester, M.L., Eastmond, N.C., Dearman, R.J., Kimber, I., Basketter, D.A., Coleman, J.W. Immunology (1999) [Pubmed]
  22. Interleukin-4 and interferon-gamma regulate differentiation of CD8+ T cells into populations with divergent cytokine profiles. Noble, A., Kemeny, D.M. Int. Arch. Allergy Immunol. (1995) [Pubmed]
  23. Cytokine expression in the presence or absence of late airway responses after antigen challenge of sensitized rats. Renzi, P.M., al Assaad, A.S., Yang, J., Yasruel, Z., Hamid, Q. Am. J. Respir. Cell Mol. Biol. (1996) [Pubmed]
  24. Interleukin-4 and IFN-gamma differentially stimulate macrophage chemoattractant protein-1 (MCP-1) and eotaxin production by intestinal epithelial cells. Winsor, G.L., Waterhouse, C.C., MacLellan, R.L., Stadnyk, A.W. J. Interferon Cytokine Res. (2000) [Pubmed]
  25. Differential regulation of expression of the MHC class II molecules RT1.B and RT1.D on rat B lymphocytes: effects of interleukin-4, interleukin-13 and interferon-gamma. Roos, A., Schilder-Tol, E.J., Chand, M.A., Claessen, N., Lakkis, F.G., Pascual, D.W., Weening, J.J., Aten, J. Immunology (1998) [Pubmed]
  26. LPS/IFN-gamma cytotoxicity in oligodendroglial cells: role of nitric oxide and protection by the anti-inflammatory cytokine IL-10. Molina-Holgado, E., Vela, J.M., Arévalo-Martín, A., Guaza, C. Eur. J. Neurosci. (2001) [Pubmed]
  27. Infiltrating CD45RC- T cells are associated with immunologic unresponsiveness induced by donor class I major histocompatibility complex antigens in rats. Yamaguchi, Y., Miyanari, N., Ichiguchi, O., Akizuki, E., Matsumura, F., Matsuda, T., Okabe, K., Liang, J., Ohshiro, H., Mori, K., Ogawa, M. Hepatology (1998) [Pubmed]
  28. Expression of interferon-gamma, interleukin-4 and interleukin-5 mRNA in the nasal mucosal membrane of rats with allergic rhinitis. El-Naggar, M.M., Ukai, K., Takeuchi, K., Sakakura, Y. Scand. J. Immunol. (1998) [Pubmed]
  29. Rat models of asthma and chronic obstructive lung disease. Martin, J.G., Tamaoka, M. Pulmonary pharmacology & therapeutics. (2006) [Pubmed]
  30. Haemophilus influenzae and Streptococcus pneumoniae induce different intracerebral mRNA cytokine patterns during the course of experimental bacterial meningitis. Diab, A., Zhu, J., Lindquist, L., Wretlind, B., Bakhiet, M., Link, H. Clin. Exp. Immunol. (1997) [Pubmed]
  31. Effect of FC43se on endotoxin-induced disseminated intravascular coagulation in rats. Ochikubo, H., Wada, S., Sugawara, Y., Sueda, T., Matsuura, Y. Hiroshima J. Med. Sci. (1999) [Pubmed]
  32. Orthodontic movement induces high numbers of cells expressing IFN-gamma at mRNA and protein levels. Alhashimi, N., Frithiof, L., Brudvik, P., Bakhiet, M. J. Interferon Cytokine Res. (2000) [Pubmed]
  33. Interleukin-10, interleukin-4, and transforming growth factor-beta differentially regulate lipopolysaccharide-induced production of pro-inflammatory cytokines and nitric oxide in co-cultures of rat astroglial and microglial cells. Ledeboer, A., Brevé, J.J., Poole, S., Tilders, F.J., Van Dam, A.M. Glia (2000) [Pubmed]
  34. Intragraft cytokine expression and tolerance induction in rat renal allografts. Saggi, B.H., Fisher, R.A., Bu, D., Tawes, J.W., Riley, R., Posner, M.P. Transplantation (1999) [Pubmed]
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