Abstract
The aim of the study was to analyse the effect of interleukin-4 (IL-4) on allergen and anti-IgE mediated histamine release from basophils and human skin mast cells and to assess whether soluble recombinant interleukin-4 receptor (sIL4R) can inhibit these effects. Anti-IgE stimulated histamine release from peripheral blood basophils and mast cells of atopic donors was enhanced after preincubation with IL-4, whereas after preincubation with sIL-4R it was inhibited. These effects were even more pronounced when samples were stimulated with a clinically relevant allergen. In IL-4 preincubated skin mast cells, there was a similar enhancement of anti-IgE stimulated histamine release, which could again be inhibited by sIL-4R. The effects of IL-4 and sIL4R were dose- and time-dependent. Mice sensitized to ovalbumin and treated with soluble recombinant murine sIL-4R showed significantly reduced immediate-type cutaneous hypersensitivity responses compared with untreated mice. These in vivo effects were IgE independent, since there were no significant differences in total and allergen specific IgE/IgG1 antibody titres between treated and untreated mice. This indicates that IL4 exerts priming effects on histamine release by effector cells of the allergic response and that these effects are potently antagonized by soluble IL-4R both in vitro and in vivo.
Full Text
The Full Text of this article is available as a PDF (218.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aoki I., Kinzer C., Shirai A., Paul W. E., Klinman D. M. IgE receptor-positive non-B/non-T cells dominate the production of interleukin 4 and interleukin 6 in immunized mice. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2534–2538. doi: 10.1073/pnas.92.7.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradding P., Feather I. H., Howarth P. H., Mueller R., Roberts J. A., Britten K., Bews J. P., Hunt T. C., Okayama Y., Heusser C. H. Interleukin 4 is localized to and released by human mast cells. J Exp Med. 1992 Nov 1;176(5):1381–1386. doi: 10.1084/jem.176.5.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunner T., Heusser C. H., Dahinden C. A. Human peripheral blood basophils primed by interleukin 3 (IL-3) produce IL-4 in response to immunoglobulin E receptor stimulation. J Exp Med. 1993 Mar 1;177(3):605–611. doi: 10.1084/jem.177.3.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casolaro V., Spadaro G., Marone G. Human basophil releasability. VI. Changes in basophil releasability in patients with allergic rhinitis or bronchial asthma. Am Rev Respir Dis. 1990 Nov;142(5):1108–1111. doi: 10.1164/ajrccm/142.5.1108. [DOI] [PubMed] [Google Scholar]
- Del Prete G., Maggi E., Parronchi P., Chrétien I., Tiri A., Macchia D., Ricci M., Banchereau J., De Vries J., Romagnani S. IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol. 1988 Jun 15;140(12):4193–4198. [PubMed] [Google Scholar]
- Dubois G. R., Bruijnzeel-Koomen C. A., Bruijnzeel P. L. IL-4 induces chemotaxis of blood eosinophils from atopic dermatitis patients, but not from normal individuals. J Invest Dermatol. 1994 Jun;102(6):843–846. doi: 10.1111/1523-1747.ep12382362. [DOI] [PubMed] [Google Scholar]
- Finkelman F. D., Katona I. M., Urban J. F., Jr, Holmes J., Ohara J., Tung A. S., Sample J. V., Paul W. E. IL-4 is required to generate and sustain in vivo IgE responses. J Immunol. 1988 Oct 1;141(7):2335–2341. [PubMed] [Google Scholar]
- Gagnon R., Lian J., Boutin Y., Hébert J. Seasonal enhancement of IL-4 induced IgE synthesis by peripheral blood mononuclear cells of atopic patients. Clin Exp Allergy. 1993 Jun;23(6):498–503. doi: 10.1111/j.1365-2222.1993.tb03237.x. [DOI] [PubMed] [Google Scholar]
- Galéa P., Thibault G., Lacord M., Bardos P., Lebranchu Y. IL-4, but not tumor necrosis factor-alpha, increases endothelial cell adhesiveness for lymphocytes by activating a cAMP-dependent pathway. J Immunol. 1993 Jul 15;151(2):588–596. [PubMed] [Google Scholar]
- Garrone P., Djossou O., Galizzi J. P., Banchereau J. A recombinant extracellular domain of the human interleukin 4 receptor inhibits the biological effects of interleukin 4 on T and B lymphocytes. Eur J Immunol. 1991 Jun;21(6):1365–1369. doi: 10.1002/eji.1830210606. [DOI] [PubMed] [Google Scholar]
- Idzerda R. L., March C. J., Mosley B., Lyman S. D., Vanden Bos T., Gimpel S. D., Din W. S., Grabstein K. H., Widmer M. B., Park L. S. Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily. J Exp Med. 1990 Mar 1;171(3):861–873. doi: 10.1084/jem.171.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jabara H. H., Ahern D. J., Vercelli D., Geha R. S. Hydrocortisone and IL-4 induce IgE isotype switching in human B cells. J Immunol. 1991 Sep 1;147(5):1557–1560. [PubMed] [Google Scholar]
- Jujo K., Renz H., Abe J., Gelfand E. W., Leung D. Y. Decreased interferon gamma and increased interleukin-4 production in atopic dermatitis promotes IgE synthesis. J Allergy Clin Immunol. 1992 Sep;90(3 Pt 1):323–331. doi: 10.1016/s0091-6749(05)80010-7. [DOI] [PubMed] [Google Scholar]
- Lack G., Renz H., Saloga J., Bradley K. L., Loader J., Leung D. Y., Larsen G., Gelfand E. W. Nebulized but not parenteral IFN-gamma decreases IgE production and normalizes airways function in a murine model of allergen sensitization. J Immunol. 1994 Mar 1;152(5):2546–2554. [PubMed] [Google Scholar]
- Larsen G. L., Renz H., Loader J. E., Bradley K. L., Gelfand E. W. Airway response to electrical field stimulation in sensitized inbred mice. Passive transfer of increased responsiveness with peribronchial lymph nodes. J Clin Invest. 1992 Mar;89(3):747–752. doi: 10.1172/JCI115651. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lebman D. A., Coffman R. L. Interleukin 4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures. J Exp Med. 1988 Sep 1;168(3):853–862. doi: 10.1084/jem.168.3.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lichey J., Zuberbier T., Luck W., Lau S., Wahn U. Influence of glycosphingolipids on the release of histamine and sulfidopeptide leukotrienes from human basophils. Int Arch Allergy Immunol. 1994;103(3):252–259. doi: 10.1159/000236636. [DOI] [PubMed] [Google Scholar]
- Lowman M. A., Rees P. H., Benyon R. C., Church M. K. Human mast cell heterogeneity: histamine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-dependent and nonimmunologic stimuli. J Allergy Clin Immunol. 1988 Mar;81(3):590–597. [PubMed] [Google Scholar]
- Maliszewski C. R., Sato T. A., Vanden Bos T., Waugh S., Dower S. K., Slack J., Beckmann M. P., Grabstein K. H. Cytokine receptors and B cell functions. I. Recombinant soluble receptors specifically inhibit IL-1- and IL-4-induced B cell activities in vitro. J Immunol. 1990 Apr 15;144(8):3028–3033. [PubMed] [Google Scholar]
- Mosley B., Beckmann M. P., March C. J., Idzerda R. L., Gimpel S. D., VandenBos T., Friend D., Alpert A., Anderson D., Jackson J. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. doi: 10.1016/0092-8674(89)90295-x. [DOI] [PubMed] [Google Scholar]
- Renz H., Bradley K., Enssle K., Loader J. E., Larsen G. L., Gelfand E. W. Prevention of the development of immediate hypersensitivity and airway hyperresponsiveness following in vivo treatment with soluble IL-4 receptor. Int Arch Allergy Immunol. 1996 Feb;109(2):167–176. doi: 10.1159/000237216. [DOI] [PubMed] [Google Scholar]
- Renz H., Enssle K., Lauffer L., Kurrle R., Gelfand E. W. Inhibition of allergen-induced IgE and IgG1 production by soluble IL-4 receptor. Int Arch Allergy Immunol. 1995 Jan;106(1):46–54. doi: 10.1159/000236889. [DOI] [PubMed] [Google Scholar]
- Renz H., Smith H. R., Henson J. E., Ray B. S., Irvin C. G., Gelfand E. W. Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. J Allergy Clin Immunol. 1992 Jun;89(6):1127–1138. doi: 10.1016/0091-6749(92)90296-e. [DOI] [PubMed] [Google Scholar]
- Ricci M. IL-4: a key cytokine in atopy. Clin Exp Allergy. 1994 Sep;24(9):801–812. doi: 10.1111/j.1365-2222.1994.tb01803.x. [DOI] [PubMed] [Google Scholar]
- Saloga J., Renz H., Lack G., Bradley K. L., Greenstein J. L., Larsen G., Gelfand E. W. Development and transfer of immediate cutaneous hypersensitivity in mice exposed to aerosolized antigen. J Clin Invest. 1993 Jan;91(1):133–140. doi: 10.1172/JCI116162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schleimer R. P., Sterbinsky S. A., Kaiser J., Bickel C. A., Klunk D. A., Tomioka K., Newman W., Luscinskas F. W., Gimbrone M. A., Jr, McIntyre B. W. IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J Immunol. 1992 Feb 15;148(4):1086–1092. [PubMed] [Google Scholar]
- Schroeder J. T., MacGlashan D. W., Jr, Kagey-Sobotka A., White J. M., Lichtenstein L. M. IgE-dependent IL-4 secretion by human basophils. The relationship between cytokine production and histamine release in mixed leukocyte cultures. J Immunol. 1994 Aug 15;153(4):1808–1817. [PubMed] [Google Scholar]
- Schroeder J. T., MacGlashan D. W., Jr, Kagey-Sobotka A., White J. M., Lichtenstein L. M. IgE-dependent IL-4 secretion by human basophils. The relationship between cytokine production and histamine release in mixed leukocyte cultures. J Immunol. 1994 Aug 15;153(4):1808–1817. [PubMed] [Google Scholar]
- Siraganian R. P. Refinements in the automated fluorometric histamine analysis system. J Immunol Methods. 1975 Jun;7(2-3):283–290. doi: 10.1016/0022-1759(75)90025-3. [DOI] [PubMed] [Google Scholar]
- Tang M., Kemp A., Varigos G. IL-4 and interferon-gamma production in children with atopic disease. Clin Exp Immunol. 1993 Apr;92(1):120–124. doi: 10.1111/j.1365-2249.1993.tb05957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valent P., Besemer J., Kishi K., Di Padova F., Geissler K., Lechner K., Bettelheim P. Human basophils express interleukin-4 receptors. Blood. 1990 Nov 1;76(9):1734–1738. [PubMed] [Google Scholar]
- Valent P., Bevec D., Maurer D., Besemer J., Di Padova F., Butterfield J. H., Speiser W., Majdic O., Lechner K., Bettelheim P. Interleukin 4 promotes expression of mast cell ICAM-1 antigen. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3339–3342. doi: 10.1073/pnas.88.8.3339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wahn U., Ernsting M., Peterson J. Spontaneous histamine release from washed leukocytes and whole blood in atopic and non-atopic individuals. Allergy. 1990 Feb;45(2):109–114. doi: 10.1111/j.1398-9995.1990.tb00467.x. [DOI] [PubMed] [Google Scholar]