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Gene Review

IL4  -  interleukin 4

Bos taurus

Synonyms: BSF-1, IL-4
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Disease relevance of IL4


High impact information on IL4

  • Although 10 nM IL-4 was as effective as 10 nM IGF-I in stimulating IRS-2 phosphorylation, 10 nM IL-4 did not have comparable mitogenic power in these cells [4].
  • The interleukin-4 (IL-4) cytokine receptor also has IRS-2 as its major substrate for tyrosine phosphorylation [4].
  • The 35-kDa protein also induced significant lymphocyte proliferation as well as the production of IFN-gamma and IL-4 from low and medium shedders [5].
  • Although Stx1 did not affect the natural killer cell activity of iIEL, the toxin accelerated the synthesis of interleukin-4 (IL-4) mRNA and reduced the amount of IL-8 mRNA in bovine iIEL cultures [6].
  • Stimulation of CD4(+) T cells induced similar levels of IL-2-and IL-4-like activity and interferon-gamma [7].

Biological context of IL4


Anatomical context of IL4

  • Interleukin-4 (IL4) is involved in the immune response to certain parasites and possibly in the development of some atopic diseases since it triggers the T helper 2 lymphocyte response [8].
  • The immune response seen in the abomasum is in many ways are similar to that seen other mammalian hosts, with high levels of expression of IL4 in the draining lymph nodes and in lymphocytes isolated from the mucosa [2].
  • Nonetheless, pretreatment of bovine fibroblasts with IL-4 inhibited IGF-I-stimulated DNA synthesis by 50-60%, concomitant with a decrease in IGF-I-induced IRS-2 phosphorylation [4].
  • Previous studies demonstrated that cattle immunized with native protein that were subsequently protected against challenge had a strong IFN-gamma and weaker interleukin-4 (IL-4) response in immune lymph node lymphocytes that reflected the cytokine profile of the majority of CD4(+) T-cell clones obtained from peripheral blood [13].
  • Several Th-cell clones were identified as Th2 cells by the strong expression of IL-4 but little or no IL-2 or IFN-gamma mRNA [14].

Associations of IL4 with chemical compounds

  • Because of the known signaling pathways for IL-4 and importance of calcium uptake in maintaining SR calcium stores shared by agonists and caffeine, it was hypothesized that this rapid inhibitory effect might depend on phosphatidylinositol 3-kinase (PI3K) and on inhibition of calcium uptake by the SR [12].
  • Calcium transients in response to carbachol (10 microM) were significantly decreased to 0.34 +/- 0.10 of control after 20-min treatment with IL-4 but were 1.10 +/- 0.26 and 1.08 +/- 0.23 when wortmannin or deguelin, respectively, was added along with IL-4 [12].
  • Other modulators of cellular function including phenylbutazone (PBZ, 100 microMs), flunixin meglumine (FM, 100 microMs) and interleukin-4 (IL-4, 100 ng/ml) modestly inhibited synthesis of NO, but did not improve cellular viability [15].
  • Increased bovine PPD-specific IL-4 mRNA expression in cattle, post-challenge, correlated with the presence of tuberculous lung lesions [16].

Other interactions of IL4


Analytical, diagnostic and therapeutic context of IL4


  1. Development and in vitro characterization of recombinant vaccinia viruses expressing bovine leukemia virus gp51 in combination with bovine IL4 or IL12. Von Beust, B.R., Brown, W.C., Estes, D.M., Zarlenga, D.S., McElwain, T.F., Palmer, G.H. Vaccine (1999) [Pubmed]
  2. Role of the bovine immune system and genome in resistance to gastrointestinal nematodes. Gasbarre, L.C., Leighton, E.A., Sonstegard, T. Vet. Parasitol. (2001) [Pubmed]
  3. Distinct response kinetics of gamma interferon and interleukin-4 in bovine tuberculosis. Rhodes, S.G., Palmer, N., Graham, S.P., Bianco, A.E., Hewinson, R.G., Vordermeier, H.M. Infect. Immun. (2000) [Pubmed]
  4. Insulin and interleukin-4 induce desensitization to the mitogenic effects of insulin-like growth factor-I. Pivotal role for insulin receptor substrate-2. Haddad, T.C., Conover, C.A. J. Biol. Chem. (1997) [Pubmed]
  5. In vitro cellular immune responses to recombinant antigens of Mycobacterium avium subsp. paratuberculosis. Shin, S.J., Chang, C.F., Chang, C.D., McDonough, S.P., Thompson, B., Yoo, H.S., Chang, Y.F. Infect. Immun. (2005) [Pubmed]
  6. Bovine ileal intraepithelial lymphocytes represent target cells for Shiga toxin 1 from Escherichia coli. Menge, C., Blessenohl, M., Eisenberg, T., Stamm, I., Baljer, G. Infect. Immun. (2004) [Pubmed]
  7. Cytokine responses of bovine dendritic cells and T cells following exposure to live or inactivated bovine respiratory syncytial virus. Werling, D., Collins, R.A., Taylor, G., Howard, C.J. J. Leukoc. Biol. (2002) [Pubmed]
  8. The bovine interleukin-4 gene: genomic organization, localization, and evolution. Buitkamp, J., Schwaiger, F.W., Solinas-Toldo, S., Fries, R., Epplen, J.T. Mamm. Genome (1995) [Pubmed]
  9. A microsatellite (BOBT24) located between the bovine IL4 and IL13 loci is polymorphic in cattle and goat. Buitkamp, J., Obexer-Ruff, G., Kessler, M., Epplen, J.T. Anim. Genet. (1996) [Pubmed]
  10. Down-regulated lymphoproliferation coincides with parasite maturation and with the collapse of both gamma interferon and interleukin-4 responses in a bovine model of onchocerciasis. Graham, S.P., Trees, A.J., Collins, R.A., Moore, D.M., Guy, F.M., Taylor, M.J., Bianco, A.E. Infect. Immun. (2001) [Pubmed]
  11. A novel protein expression strategy using recombinant bovine respiratory syncytial virus (BRSV): modifications of the peptide sequence between the two furin cleavage sites of the BRSV fusion protein yield secreted proteins, but affect processing and function of the BRSV fusion protein. König, P., Giesow, K., Schuldt, K., Buchholz, U.J., Keil, G.M. J. Gen. Virol. (2004) [Pubmed]
  12. Mechanisms of interleukin-4 effects on calcium signaling in airway smooth muscle cells. Ethier, M.F., Cappelluti, E., Madison, J.M. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  13. Bovine CD4(+) T-lymphocyte clones specific for rhoptry-associated protein 1 of Babesia bigemina stimulate enhanced immunoglobulin G1 (IgG1) and IgG2 synthesis. Brown, W.C., McElwain, T.F., Palmer, G.H., Chantler, S.E., Estes, D.M. Infect. Immun. (1999) [Pubmed]
  14. CD4+ T-cell clones obtained from cattle chronically infected with Fasciola hepatica and specific for adult worm antigen express both unrestricted and Th2 cytokine profiles. Brown, W.C., Davis, W.C., Dobbelaere, D.A., Rice-Ficht, A.C. Infect. Immun. (1994) [Pubmed]
  15. Bacterial lipopolysaccharide-stimulated nitric oxide generation is unrelated to concurrent cytotoxicity of bovine alveolar macrophages. Bochsler, P.N., Mason, G.L., Olchowy, T.W., Yang, Z. Inflammation (1996) [Pubmed]
  16. Vaccination with DNA vaccines encoding MPB70 or MPB83 or a MPB70 DNA prime-protein boost does not protect cattle against bovine tuberculosis. Wedlock, D.N., Skinner, M.A., Parlane, N.A., Vordermeier, H.M., Hewinson, R.G., de Lisle, G.W., Buddle, B.M. Tuberculosis (Edinburgh, Scotland) (2003) [Pubmed]
  17. Characterization of protective immune responses in local lymphoid tissues after drug-attenuated infections with Ostertagia ostertagi in calves. Almería, S., Canals, A., Gómez-Muñoz, M.T., Zarlenga, D.S., Gasbarre, L.C. Vet. Parasitol. (1998) [Pubmed]
  18. Cryptosporidium parvum infection in bovine neonates: dynamic clinical, parasitic and immunologic patterns. Fayer, R., Gasbarre, L., Pasquali, P., Canals, A., Almeria, S., Zarlenga, D. Int. J. Parasitol. (1998) [Pubmed]
  19. Cloning of a full-length cDNA encoding bovine interleukin 4 by the polymerase chain reaction. Heussler, V.T., Eichhorn, M., Dobbelaere, D.A. Gene (1992) [Pubmed]
  20. Efficacy of a pour-on formulation of eprinomectin (MK-397) against nematode parasites of cattle, with emphasis on inhibited early fourth-stage larvae of Ostertagia spp. Williams, J.C., Stuedemann, J.A., Bairden, K., Kerboeuf, D., Ciordia, H., Hubert, J., Broussard, S.D., Plue, R.E., Alva-Valdes, R., Baggott, D.G., Pinkall, N., Eagleson, J.S. Am. J. Vet. Res. (1997) [Pubmed]
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