Gene Symbol: IL-4
Description: interleukin 4
Alias: BCGF-1, BCGF1, BSF-1, BSF1, IL-4, interleukin-4, B cell growth factor 1, B_cell stimulatory factor 1, binetrakin, interleukin 4 variant 2, lymphocyte stimulatory factor 1, pitrakinra
Species: human
Products:     IL-4

Top Publications

  1. Nguyen D, Genc M, Vardhana S, Babula O, Onderdonk A, Witkin S. Ethnic differences of polymorphisms in cytokine and innate immune system genes in pregnant women. Obstet Gynecol. 2004;104:293-300 pubmed
    ..007) or blacks (P =.02). Investigations of the role of genetic factors affecting pregnancy outcome must be cognizant of ethnic variations when enrolling case and control subjects for studies on allele and genotype frequencies. ..
  2. Vasudevan R, Norhasniza M, Patimah I. Association of variable number of tandem repeats polymorphism in the IL-4 gene with end-stage renal disease in Malaysian patients. Genet Mol Res. 2011;10:943-7 pubmed publisher
    Variable number of tandem repeats (VNTR) polymorphism in the interleukin 4 (IL-4) gene has been associated with end-stage renal disease (ESRD) subjects in many different populations, although with conflicting results...
  3. Zheng Z, Li X, Li Z, Ma X. IL-4 -590C/T polymorphism and susceptibility to liver disease: a meta-analysis and meta-regression. DNA Cell Biol. 2013;32:443-50 pubmed publisher
    ..In conclusion, the current meta-analysis indicates that the IL-4 -590T polymorphism may play an important role in increasing HBV and HCV infection risks, especially among Caucasian populations. ..
  4. Inanir A, Yigit S, Tekcan A, Tural S, Kismali G. IL-4 and MTHFR gene polymorphism in rheumatoid arthritis and their effects. Immunol Lett. 2013;152:104-8 pubmed publisher
    ..Our findings suggest that there is an association of IL-4 gene 70bp VNTR polymorphism and MTHFR C677T polymorphism with susceptibility of a person for development of RA. ..
  5. Konwar R, Chaudhary P, Kumar S, Mishra D, Chattopadhyay N, Bid H. Breast cancer risk associated with polymorphisms of IL-1RN and IL-4 gene in Indian women. Oncol Res. 2009;17:367-72 pubmed
    ..Further studies in other population are needed to confirm our findings and to elucidate the role of IL-1RN in progression of breast cancer. ..
  6. Sobti R, Maithil N, Thakur H, Sharma Y, Talwar K. VEGF and IL-4 gene variability and its association with the risk of coronary heart disease in north Indian population. Mol Cell Biochem. 2010;341:139-48 pubmed publisher
    ..34, 95% CI 0.14-0.82, P < 0.01) and central obesity (OR 0.15, 95% CI 0.04-0.56, P < 0.001). GG genotype of VEGF has also shown significant association with IL-4 (P2P2 and P1P2) genotypes. ..
  7. Li H, Xiaoyan D, Quanhua L, Jie L, Yixiao B. Single-nucleotide polymorphisms in genes predisposing to asthma in children of Chinese Han nationality. J Investig Allergol Clin Immunol. 2009;19:391-5 pubmed
    ..FcepsilonR1beta C-109T and beta2-ADR R16G are significantly associated with childhood asthma. FcepsilonR1beta C-109T T/T and beta2-ADR R16G A/A have a significant and combined effect on the development of asthma. ..
  8. Forbes E, van Panhuys N, Min B, Le Gros G. Differential requirements for IL-4/STAT6 signalling in CD4 T-cell fate determination and Th2-immune effector responses. Immunol Cell Biol. 2010;88:240-3 pubmed publisher
  9. Gao Q, Liu D, Zhang S, Jia M, Wang L, Wu L, et al. Polymorphisms of some cytokines and chronic hepatitis B and C virus infection. World J Gastroenterol. 2009;15:5610-9 pubmed
    ..These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage. ..

More Information


  1. Shahram F, Nikoopour E, Rezaei N, Saeedfar K, Ziaei N, Davatchi F, et al. Association of interleukin-2, interleukin-4 and transforming growth factor-beta gene polymorphisms with Behcet's disease. Clin Exp Rheumatol. 2011;29:S28-31 pubmed
    ..Cytokine single nucleotide polymorphisms could play a role in the pathophysiology of BD. The results of this study could suggest a tendency towards higher production of IL-2 and lower production of IL-4 in the patients with BD. ..
  2. Anovazzi G, Kim Y, Viana A, Curtis K, Orrico S, Cirelli J, et al. Polymorphisms and haplotypes in the interleukin-4 gene are associated with chronic periodontitis in a Brazilian population. J Periodontol. 2010;81:392-402 pubmed publisher
    ..Significant associations between alleles, genotypes, and haplotypes of polymorphisms in the IL4 gene and chronic periodontitis were verified in Brazilian individuals. ..
  3. Shekari M, Kordi Tamandani D, Malekzadeh K, Sobti R, Karimi S, Suri V. Effect of anti-inflammatory (IL-4, IL-10) cytokine genes in relation to risk of cervical carcinoma. Am J Clin Oncol. 2012;35:514-9 pubmed publisher
    ..This study suggests that passive smokers among North Indian women having IL-4 Rp1/Rp2 and IL-10 (AC) genotypes had an increased risk for developing cervical cancer. ..
  4. Oral H, Dilek K, Ozçimen A, Taskapilioglu O, Bingol U, Sarandol A, et al. Interleukin-4 gene polymorphisms confer Behçet's disease in Turkish population. Scand J Immunol. 2011;73:594-601 pubmed publisher
    ..However, in order to confirm and assess the association of IL-4 and IL-4R? gene polymorphisms with the BD, large cohort studies are needed. ..
  5. Cabantous S, Poudiougou B, Oumar A, Traore A, Barry A, Vitte J, et al. Genetic evidence for the aggravation of Plasmodium falciparum malaria by interleukin 4. J Infect Dis. 2009;200:1530-9 pubmed publisher
    ..Here, we investigated whether interleukin 4 (IL-4) aggravates the risk of severe disease...
  6. Gervaziev Y, Olenina L, Krasotkina J, Lupatov A, Mazurina S, Gervazieva V. Oct-1 is responsible for the C-33T polymorphism effect in the IL-4 promoter. Int J Immunogenet. 2010;37:13-20 pubmed publisher
    ..Our findings suggest that the interplay between Oct-1 and unknown TFs may be responsible for the C-33T polymorphism effects. ..
  7. Vafa M, Maiga B, Israelsson E, Dolo A, Doumbo O, Troye Blomberg M. Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali. Microbes Infect. 2009;11:779-84 pubmed publisher
    ..Taken together, these data indicate that the impact of IL-4 -590 variants on antibody levels may vary in different ethnic populations, and that this might affect the Ig-class and subclass distributions. ..
  8. Yakeu G, Butcher L, Isa S, Webb R, Roberts A, Thomas A, et al. Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: roles of PPAR? and Th2 cytokines. Atherosclerosis. 2010;212:668-73 pubmed publisher
  9. Eid N, Hussein A, Elzein A, Mohamed H, Rockett K, Kwiatkowski D, et al. Candidate malaria susceptibility/protective SNPs in hospital and population-based studies: the effect of sub-structuring. Malar J. 2010;9:119 pubmed publisher
  10. Tangteerawatana P, Perlmann H, Hayano M, Kalambaheti T, Troye Blomberg M, Khusmith S. IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria. Malar J. 2009;8:286 pubmed publisher
  11. Naslednikova I, Urazova O, Voronkova O, Strelis A, Novitsky V, Nikulina E, et al. Allelic polymorphism of cytokine genes during pulmonary tuberculosis. Bull Exp Biol Med. 2009;148:175-80 pubmed
  12. Krabben A, Wilson A, de Rooy D, Zhernakova A, Brouwer E, Lindqvist E, et al. Association of genetic variants in the IL4 and IL4R genes with the severity of joint damage in rheumatoid arthritis: a study in seven cohorts. Arthritis Rheum. 2013;65:3051-7 pubmed publisher
    ..02] and rs1119132 [P = 0.001]). Genetic variants in IL4R were identified, and their association with the progression rate of joint damage in RA was independently replicated. ..
  13. Chatterjee A, Rathore A, Dhole T. Association of IL-4 589 C/T promoter and IL-4RalphaI50V receptor polymorphism with susceptibility to HIV-1 infection in North Indians. J Med Virol. 2009;81:959-65 pubmed publisher
    The clinical course and outcome of HIV-1 infection are highly variable among individuals. Interleukin 4 (IL-4) is a key T helper 2 cytokine with various immune-modulating functions including induction of immunoglobulin E (IgE) production ..
  14. Ho K, Shiau M, Chang Y, Chen C, Yang S, Huang C. Association of interleukin-4 promoter polymorphisms in Taiwanese patients with type 2 diabetes mellitus. Metabolism. 2010;59:1717-22 pubmed publisher
    ..The above results suggested that IL-4 may participate in lipid metabolism and diabetic susceptibility. ..
  15. Liu X, Wang G, Hong X, Wang D, Tsai H, Zhang S, et al. Gene-vitamin D interactions on food sensitization: a prospective birth cohort study. Allergy. 2011;66:1442-8 pubmed publisher
    ..Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene-vitamin D interaction on FS. ..
  16. YANG X, LI F, Wu Y, Wu D, Tan J, Li M. Association of TGF-beta1, IL-4 and IL-13 gene polymerphisms with asthma in a Chinese population. Asian Pac J Allergy Immunol. 2011;29:273-7 pubmed
  17. Fang G, Fan X, Shen F. The relationship between polymorphisms of interleukin-4 gene and silicosis. Biomed Environ Sci. 2011;24:678-82 pubmed publisher
    ..7% and in the controls were 69.4%, 4.1%, and 26.4%. The differences were significant (P=0.034). The relationship between genetic polymorphism of IL-4-33 site and silicosis has been found and -33TT is a protective genotype for silicosis. ..
  18. Jha A, Singh V, Kumari N, Singh A, Antony J, Van Tong H, et al. IL-4 haplotype -590T, -34T and intron-3 VNTR R2 is associated with reduced malaria risk among ancestral indian tribal populations. PLoS ONE. 2012;7:e48136 pubmed publisher
    b>Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between T(H)1 and T(H)2 immune response, immunoglobulin class switching and humoral immunity...
  19. Hussein Y, El Shal A, Rezk N, Abdel Galil S, Alzahrani S. Influence of interleukin-4 gene polymorphisms and interleukin-4 serum level on susceptibility and severity of rheumatoid arthritis in Egyptian population. Cytokine. 2013;61:849-55 pubmed publisher
    ..IL-4 VNTR and IL-4-590 promoter polymorphisms may be helpful for assessing RA severity in Egyptian population. Moreover, IL-4-590 promoter polymorphism may be associated with increased risk and activity of RA. ..
  20. Yang H. Association between the interleukin-4 gene C-589T and C+33T polymorphisms and asthma risk: a meta-analysis. Arch Med Res. 2013;44:127-35 pubmed publisher
    ..036 [1.224-7.529]), and children (OR [95% CI] = 1.300 [1.075-1.573]) in a recessive genetic model. This meta-analysis suggests that the IL-4 C-589T and C+33T polymorphisms may be risk factors for asthma. ..
  21. Inanir A, Tural S, Yigit S, Kalkan G, Pancar G, Demir H, et al. Association of IL-4 gene VNTR variant with deep venous thrombosis in Behçet's disease and its effect on ocular involvement. Mol Vis. 2013;19:675-83 pubmed
    ..Deep venous thrombosis is also associated with ocular involvement in BD. The IL-4 gene could be a genetic biomarker in Behçet's disease in a Turkish study population. ..
  22. Cui W, Sun C, Deng B, Liu P. Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: a meta-analysis. Gene. 2013;525:35-40 pubmed publisher
    ..The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection...
  23. Song G, Bae S, Kim J, Lee Y. Interleukin-4, interleukin-4 receptor, and interleukin-18 polymorphisms and rheumatoid arthritis: a meta-analysis. Immunol Invest. 2013;42:455-69 pubmed publisher
    ..This meta-analysis demonstrates that the IL-4 -590 T/C polymorphism is associated with susceptibility to RA in Europeans, but the IL-4R?+?1902 G/A, IL-18 -607 C/A and -137 G/C polymorphisms are not associated with RA. ..
  24. Black S, Teixeira A, Loh A, Vinall L, Holloway J, Hardy R, et al. Contribution of functional variation in the IL13 gene to allergy, hay fever and asthma in the NSHD longitudinal 1946 birth cohort. Allergy. 2009;64:1172-8 pubmed publisher
    ..In a longitudinal population cohort we have established a role for polymorphism of IL13 in determining susceptibility to both atopy and asthma. ..
  25. Zhu Q, Ge Y, Gu S, Yu H, Wang J, Gu X, et al. Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection. Chin Med J (Engl). 2005;118:1604-9 pubmed
    ..There was no evident relationship between IL-4 -590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10 -1082 G allele was associated with preventive efficacy to HBV intrauterine infection. ..
  26. Kantarci O, Schaefer Klein J, Hebrink D, Achenbach S, Atkinson E, McMurray C, et al. A population-based study of IL4 polymorphisms in multiple sclerosis. J Neuroimmunol. 2003;137:134-9 pubmed
    ..54). We could not confirm the previously reported association between carriage of I3(709)*allele-2 and older age of onset. However, we found a trend for association between the homozygous state for this allele and older age of onset. ..
  27. Ohashi J, Naka I, Patarapotikul J, Hananantachai H, Looareesuwan S, Tokunaga K. A single-nucleotide substitution from C to T at position -1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand. Genes Immun. 2003;4:528-31 pubmed
    ..An IL-13 -1055C>T has been reported to alter the regulation of IL-13 production. Thus, IL-13 -1055T may show resistance to severe malaria through the alteration of IL-13 production. ..
  28. Vidyarani M, Selvaraj P, Prabhu Anand S, Jawahar M, Adhilakshmi A, Narayanan P. Interferon gamma (IFNgamma) & interleukin-4 (IL-4) gene variants & cytokine levels in pulmonary tuberculosis. Indian J Med Res. 2006;124:403-10 pubmed
    ..The higher frequency of IL-4 'CT' genotype in PTB suggests a possible association of IL-4 -590T promoter polymorphism with susceptibility to tuberculosis, and the 'CC' genotype may be associated with protection. ..
  29. Kim J, Cheon I, Won Y, Na H, Kim Y, Choe J. IL-4 inhibits cell cycle progression of human umbilical vein endothelial cells by affecting p53, p21(Waf1), cyclin D1, and cyclin E expression. Mol Cells. 2003;16:92-6 pubmed
    ..These results show that IL-4 inhibits endothelial cell growth by altering the expression of cell cycle regulatory molecules. ..
  30. Lee S, Pinder E, Chun J, Lou W, Sun M, Gao A. Interleukin-4 stimulates androgen-independent growth in LNCaP human prostate cancer cells. Prostate. 2008;68:85-91 pubmed
    ..These studies suggest that IL-4 plays an important role in promoting androgen-independent prostate cancer growth. ..
  31. Gervaziev Y, Kaznacheev V, Gervazieva V. Allelic polymorphisms in the interleukin-4 promoter regions and their association with bronchial asthma among the Russian population. Int Arch Allergy Immunol. 2006;141:257-64 pubmed
    ..Our data suggest that IL-4 promoter polymorphism in the Russian population might play a role both conferring susceptibility to BA and modulating the levels of serum IL-4 and total IgE. ..
  32. Genevay S, di Giovine F, Perneger T, Silvestri T, Stingelin S, Duff G, et al. Association of interleukin-4 and interleukin-1B gene variants with Larsen score progression in rheumatoid arthritis. Arthritis Rheum. 2002;47:303-9 pubmed
    ..001). None of the markers tested were shown to be associated with increased or decreased risk of RA. The rarer alleles of IL-4 VNTR and IL-1B (-511) appear to be associated with a less severe course in RA of long duration. ..
  33. Ognjanovic S, Yuan J, Chaptman A, Fan Y, Yu M. Genetic polymorphisms in the cytokine genes and risk of hepatocellular carcinoma in low-risk non-Asians of USA. Carcinogenesis. 2009;30:758-62 pubmed publisher
    ..98, 95% CI = 0.50-7.84, P = 0.08). In contrast to high-risk Chinese, Th1 and Th2 genotypes did not impact in a major way on risk of HCC in USA non-Asians. ..
  34. Guenova E, Volz T, Sauer K, Kaesler S, Muller M, Wölbing F, et al. IL-4-mediated fine tuning of IL-12p70 production by human DC. Eur J Immunol. 2008;38:3138-49 pubmed publisher
    ..Thus, we demonstrate that the Th2 cell cytokine IL-4 decisively determines the phenotype of ongoing immune responses by orchestrating the functional phenotype of newly immigrating DC precursors. ..
  35. Aithal G, Ramsay L, Daly A, Sonchit N, Leathart J, Alexander G, et al. Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity. Hepatology. 2004;39:1430-40 pubmed
    ..In conclusion, the observed polymorphisms, resulting in low IL-10 and high IL-4 gene transcription, could favor a T helper (Th)-2 mediated antibody response to neoantigenic stimulation associated with disease susceptibility. ..
  36. Gyan B, Goka B, Cvetkovic J, Kurtzhals J, Adabayeri V, Perlmann H, et al. Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children. Clin Exp Immunol. 2004;138:145-50 pubmed
    ..Carriers of IL-4 +33T/-590T with cerebral malaria had elevated total IgE compared to non-carriers (P = 0.03). Our data suggest that IL-4 and/or IgE play a regulatory role in the pathogenesis of severe or complicated malaria. ..
  37. Verra F, Luoni G, Calissano C, Troye Blomberg M, Perlmann P, Perlmann H, et al. IL4-589C/T polymorphism and IgE levels in severe malaria. Acta Trop. 2004;90:205-9 pubmed
    ..These results raise the possibility that there is a relationship between susceptibility to severe malaria, IgE production and genetic variation in the IL4 region, which merits further investigation in other epidemiological settings. ..
  38. Wu S, Chang J, Wan L, Tsai C, Tsai F. Association of IL-1Ra gene polymorphism, but no association of IL-1beta and IL-4 gene polymorphisms, with Kawasaki disease. J Clin Lab Anal. 2005;19:99-102 pubmed
    ..The genotype I/II for IL1-Ra and the frequency of allele II for IL1-Ra are associated with a higher susceptibility to KD, and thus may be useful markers for predicting the development of KD. ..
  39. Tangteerawatana P, Pichyangkul S, Hayano M, Kalambaheti T, Looareesuwan S, Troye Blomberg M, et al. Relative levels of IL4 and IFN-gamma in complicated malaria: association with IL4 polymorphism and peripheral parasitemia. Acta Trop. 2007;101:258-65 pubmed
    ..283, p=0.046). These results suggest that the IL4-590 C/T polymorphism may play a role in the balance between IL4 and IFN-gamma, as well as in the control of parasitemia, which in turn may alter the severity of malaria. ..
  40. Cui T, Wu J, Pan S, Xie J. Polymorphisms in the IL-4 and IL-4R [alpha] genes and allergic asthma. Clin Chem Lab Med. 2003;41:888-92 pubmed
    ..16; p < 0.01), and also total plasma immunoglobulin E (IgE) level was increased in allergic asthma patients. These data suggest that the IL-4R alpha chain 576R/R genotypes confer genetic susceptibility to allergic asthma in Chinese. ..
  41. Holla L, Fassmann A, Augustin P, Halabala T, Znojil V, Vanek J. The association of interleukin-4 haplotypes with chronic periodontitis in a Czech population. J Periodontol. 2008;79:1927-33 pubmed
    ..85; 95% confidence interval: 1.19 to 2.87). The three polymorphisms in the IL-4 gene act in a cooperative fashion and suggest that the high-production IL-4 haplotype was associated with an increased risk for CP in the Czech population. ..
  42. Zhang J, Simeonowa I, Wang Y, Sebald W. The high-affinity interaction of human IL-4 and the receptor alpha chain is constituted by two independent binding clusters. J Mol Biol. 2002;315:399-407 pubmed
    ..These results show that the high-affinity IL-4/IL4-BP contact is constituted by two independent binding units, each containing a central polar or charged side-chain surrounded by hydrophobic groups (avocado cluster). ..
  43. Powers R, Garrett D, March C, Frieden E, Gronenborn A, Clore G. Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy. Science. 1992;256:1673-7 pubmed
  44. Hage T, Sebald W, Reinemer P. Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface. Cell. 1999;97:271-81 pubmed
    ..Novel insights on ligand binding in the cytokine receptor family and a paradigm for receptors of IL-2, IL-7, IL-9, and IL-15, which all utilize gamma c, are provided. ..
  45. Cui T, Wang L, Wu J, Hu L, Xie J. Polymorphisms of IL-4, IL-4R alpha, and AICDA genes in adult allergic asthma. J Huazhong Univ Sci Technolog Med Sci. 2003;23:134-7 pubmed
    ..127, respectively; P < 0.01)] and was correlated with the increased plasma total IgE. These data suggested that the IL-4R alpha chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergic asthma in China. ..
  46. Rezaei N, Aghamohammadi A, Mahmoudi M, Shakiba Y, Kardar G, Mahmoudi M, et al. Association of IL-4 and IL-10 gene promoter polymorphisms with common variable immunodeficiency. Immunobiology. 2010;215:81-7 pubmed publisher
    ..High production of IL-4 could also be expected based on haplotypes frequencies of this cytokine gene polymorphisms...
  47. Elser B, Lohoff M, Kock S, Giaisi M, Kirchhoff S, Krammer P, et al. IFN-gamma represses IL-4 expression via IRF-1 and IRF-2. Immunity. 2002;17:703-12 pubmed
    ..Our data demonstrate a direct negative feedback of IFN-gamma on expression of the Th2 cytokine gene IL-4 and, thus, provide evidence for another important mechanism by which IFNgamma assists Th1 and attenuates Th2 responses. ..
  48. Uboldi de Capei M, Dametto E, Fasano M, Messina M, Pratico L, Rendine S, et al. Cytokines and chronic rejection: a study in kidney transplant long-term survivors. Transplantation. 2004;77:548-52 pubmed
  49. Scheurer M, Amirian E, Cao Y, Gilbert M, Aldape K, Kornguth D, et al. Polymorphisms in the interleukin-4 receptor gene are associated with better survival in patients with glioblastoma. Clin Cancer Res. 2008;14:6640-6 pubmed publisher
    ..These findings indicate that polymorphisms in inflammation pathway genes may play an important role in glioma survival. Further research on the effects of these polymorphisms on glioma prognosis is warranted. ..
  50. Suppiah V, Goris A, Alloza I, Heggarty S, Dubois B, Carton H, et al. Polymorphisms in the interleukin-4 and IL-4 receptor genes and multiple sclerosis: a study in Spanish-Basque, Northern Irish and Belgian populations. Int J Immunogenet. 2005;32:383-8 pubmed
    ..Disease or genetic heterogeneity or both may be responsible for the observed lack of reproduction in different populations. Our data reinforce recent findings for a role of IL4-R in susceptibility to MS. ..
  51. Walch L, Massade L, Dufilho M, Brunet A, Rendu F. Pro-atherogenic effect of interleukin-4 in endothelial cells: modulation of oxidative stress, nitric oxide and monocyte chemoattractant protein-1 expression. Atherosclerosis. 2006;187:285-91 pubmed
    ..These results are in favor of a pro-inflammatory and pro-atherogenic effect of IL-4 in vascular tissues. ..
  52. Beghe B, Barton S, Rorke S, Peng Q, Sayers I, Gaunt T, et al. Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population. Clin Exp Allergy. 2003;33:1111-7 pubmed
    ..006). Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma. ..
  53. Fraser R, Walker J, Ekbote U, Martin K, McShane P, Orsi N. Interleukin-4 -590 (C>T), toll-like receptor-2 +2258 (G>A) and matrix metalloproteinase-9 -1562 (C>T) polymorphisms in pre-eclampsia. BJOG. 2008;115:1052-6; discussion 1056 pubmed publisher
    ..87, P = 0.055), with a prevalence of TT homozygous women in this group (OR 4.455, 95% CI 1.286-15.350). ..
  54. Ueta M, Sotozono C, Inatomi T, Kojima K, Hamuro J, Kinoshita S. Association of combined IL-13/IL-4R signaling pathway gene polymorphism with Stevens-Johnson syndrome accompanied by ocular surface complications. Invest Ophthalmol Vis Sci. 2008;49:1809-13 pubmed publisher
    ..They also reveal that combined polymorphisms in the IL-13/IL-4R signaling pathway were associated with SJS/TEN with ocular surface complications. ..
  55. Wu M, Huang C, Tsai J, Chen H, Tsai F. Polymorphisms of the interleukin-4 gene in chinese patients with systemic lupus erythematosus in Taiwan. Lupus. 2003;12:21-5 pubmed
    ..The role of the intron 3 polymorphism of the IL4 gene in SLE remains unclear and further substantiation based on larger patient samples is needed. ..
  56. Kabesch M, Tzotcheva I, Carr D, Höfler C, Weiland S, Fritzsch C, et al. A complete screening of the IL4 gene: novel polymorphisms and their association with asthma and IgE in childhood. J Allergy Clin Immunol. 2003;112:893-8 pubmed
    ..These results indicate a possible involvement of SNPs in the IL4 gene in the development of asthma and the regulation of total serum IgE. ..
  57. Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland S, et al. IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol. 2006;117:269-74 pubmed
    ..054). These data indicate that only the combined analyses of genetic alterations in the IL-4/IL-13 pathway reveal its actual significance to the development of atopy and childhood asthma. ..
  58. Puthothu B, Krueger M, Forster J, Heinzmann A. Association between severe respiratory syncytial virus infection and IL13/IL4 haplotypes. J Infect Dis. 2006;193:438-41 pubmed
    ..More studies are needed to clarify whether RSV infection provokes asthma or whether RSV infection occurs in children who are genetically predisposed to a pronounced T helper 2 immune response and subsequently develop bronchial asthma. ..
  59. Bugawan T, Mirel D, Valdes A, Panelo A, Pozzilli P, Erlich H. Association and interaction of the IL4R, IL4, and IL13 loci with type 1 diabetes among Filipinos. Am J Hum Genet. 2003;72:1505-14 pubmed
    ..Our data suggest that the risk for T1D is determined, in part, by polymorphisms within the IL4R locus, including promoter and coding-sequence variants, and by specific combinations of genotypes at the IL4R and the IL4 and IL13 loci. ..
  60. Nakashima H, Miyake K, Inoue Y, Shimizu S, Akahoshi M, Tanaka Y, et al. Association between IL-4 genotype and IL-4 production in the Japanese population. Genes Immun. 2002;3:107-9 pubmed
    ..These results make it likely that IL-4 genotype could influence the type of immune response. ..
  61. Choi E, Lee H, Yoo T, Chanock S. A common haplotype of interleukin-4 gene IL4 is associated with severe respiratory syncytial virus disease in Korean children. J Infect Dis. 2002;186:1207-11 pubmed
  62. Poole K, Gibbs P, Evans P, Sadek S, Howell W. Influence of patient and donor cytokine genotypes on renal allograft rejection: evidence from a single centre study. Transpl Immunol. 2001;8:259-65 pubmed
    ..However, due to conflicting results from this and other studies, a multi-centre collaborative study may be required to determine whether cytokine genotypes are significant, independent predictors of renal allograft rejection. ..
  63. Aithal G, Day C, Leathart J, Daly A, Hudson M. Association of single nucleotide polymorphisms in the interleukin-4 gene and interleukin-4 receptor gene with Crohn's disease in a British population. Genes Immun. 2001;2:44-7 pubmed
    ..005). Association with alleles resulting in high IL-4 transcription and enhanced signalling activity suggests that IL-4 may have a role in the pathogenesis of Crohn's disease. ..
  64. Grunig G, Warnock M, Wakil A, Venkayya R, Brombacher F, Rennick D, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282:2261-3 pubmed
    ..This pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL-4 receptor. ..
  65. Gauchat J, Schlagenhauf E, Feng N, Moser R, Yamage M, Jeannin P, et al. A novel 4-kb interleukin-13 receptor alpha mRNA expressed in human B, T, and endothelial cells encoding an alternate type-II interleukin-4/interleukin-13 receptor. Eur J Immunol. 1997;27:971-8 pubmed
  66. Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, et al. Essential role of Stat6 in IL-4 signalling. Nature. 1996;380:627-30 pubmed
    ..These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses. ..
  67. Smith L, Redfield C, Boyd J, Lawrence G, Edwards R, Smith R, et al. Human interleukin 4. The solution structure of a four-helix bundle protein. J Mol Biol. 1992;224:899-904 pubmed
    ..m.r.) techniques have been used to determine the solution structure of human interleukin 4, a four-helix bundle protein...
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    ..These findings may provide useful information for the development of therapeutic strategies aimed at restoring the functionality of apoptotic pathways in tumor cells. ..
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    ..These observations have important implications for the regulation of epithelial cell activation by the balance of Th1/Th2-type cytokines in the airways in allergic disease. ..
  71. Pawlik A, Wrzesniewska J, Florczak M, Gawronska Szklarz B, Herczynska M. The -590 IL-4 promoter polymorphism in patients with rheumatoid arthritis. Rheumatol Int. 2005;26:48-51 pubmed
    ..We suggest that the IL-4 -590 promoter polymorphism may be a genetic risk factor for RA severity. ..
  72. Babula O, Lazdane G, Kroica J, Linhares I, Ledger W, Witkin S. Frequency of interleukin-4 (IL-4) -589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis. Clin Infect Dis. 2005;40:1258-62 pubmed
    ..Associations between this polymorphism and recurrent vulvovaginal candidiasis (RVVC), as well as vaginal concentrations of IL-4 and the anticandidal compounds nitric oxide (NO) and mannose binding lectin (MBL), were evaluated...
  73. Amirzargar M, Yavangi M, Basiri A, Moghadam S, Khosravi F, Solgi G, et al. Genetic association of interleukin-4, interleukin-10, and transforming growth factor-beta gene polymorphism with allograft function in renal transplant patients. Transplant Proc. 2007;39:954-7 pubmed
    ..TGF-beta codon 10 T allele was 39% in RE, 35% in SGF, and 53% in control group. In conclusion, this study suggested that some cytokine gene alleles reflected SGF among kidney transplant recipients. ..
  74. Hsieh Y, Chang C, Tsai C, Lin C, Tsai F. Interleukin (IL)-12 receptor beta1 codon 378 G homozygote and allele, but not IL-1 (beta-511 promoter, 3953 exon 5, receptor antagonist), IL-2 114, IL-4-590 intron 3, IL-8 3'-UTR 2767, and IL-18 105, are associated with higher susceptibility to leiom. Fertil Steril. 2007;87:886-95 pubmed
    ..The IL-1beta-511 promoter, IL-1beta exon 5, and IL-1Ra, IL-2 114, IL-4 -590 intron 3, IL-8 3'-UTR 2767, and IL-18 105 gene polymorphisms are not correlated with the development of leiomyoma. ..
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    ..Both the tertiary and secondary structures of rhuIL-4 are similar to those of human granulocyte-macrophage colony-stimulating factor. Critical regions for receptor binding are proposed. ..
  76. Wen H, Lin Y, Lee Y, Guo Y. Association between cord blood IgE and genetic polymorphisms of interleukin-4, the beta-subunit of the high-affinity receptor for IgE, lymphotoxin-alpha, and tumor necrosis factor-alpha. Pediatr Allergy Immunol. 2006;17:489-94 pubmed
    ..Our finding suggested a significant association of cbIgE with genetic polymorphism of IL-4 -590C/T, but not with the genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha. ..
  77. Zhang J, Foster D, Sebald W. Human IL-21 and IL-4 bind to partially overlapping epitopes of common gamma-chain. Biochem Biophys Res Commun. 2003;300:291-6 pubmed
    ..These results open the way to understand the molecular recognition mechanism in the IL-21 receptor system and also the promiscuous binding properties of gamma(c). ..
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    ..The C/C genotype of the IL-10 gene promoter region C592A was shown to be a factor determining resistance to long-term persistence of hepatitis B and C viruses. ..
  80. Dharancy S, Podevin P, Aoudjehane L, Batteux F, Rosenberg A, Soubrane O, et al. Elevated interleukin-4 expression in severe recurrent hepatitis C virus after liver transplantation. Transplantation. 2007;83:906-11 pubmed
    ..IL-4 expression is elevated in severe recurrent HCV and may play a role in the progression of hepatic lesions after liver transplantation. ..
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    Successful tumour immunity relies on innate and adaptive immune responses, with cytokines like interleukin 4 (IL-4) known to influence tumour clearance in both positive and negative ways...
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    ..This site-2 affinity seems to be sufficient, however, to promote, in a second step, a productive association of gamma(c) to an IL-4/alpha chain complex in the membrane. ..
  83. Tsai M, Chen W, Tsai C, Hang L, Tsai F. Interleukin-4 gene, but not the interleukin-1 beta gene polymorphism, is associated with oral cancer. J Clin Lab Anal. 2005;19:93-8 pubmed
    ..However, whether the -590 C/T polymorphism of the IL4 gene plays a role in oral cancer remains unclear. Further substantiation based on larger patient samples is needed. ..