Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Mar;87(3):870–877. doi: 10.1172/JCI115092

Glucocorticoids increase the synthesis of immunoglobulin E by interleukin 4-stimulated human lymphocytes.

C Y Wu 1, M Sarfati 1, C Heusser 1, S Fournier 1, M Rubio-Trujillo 1, R Peleman 1, G Delespesse 1
PMCID: PMC329876  PMID: 1825666

Abstract

This study indicates that hydrocortisone (HC) markedly increases the synthesis of immunoglobulin E (IgE) by interleukin 4 (IL-4)-stimulated human lymphocytes. The effect is glucocorticoid specific and is obtained with low concentrations of HC (0.1-10 microM). In both the early and the late phase of the IL-4-induced response HC exerts its effects which are respectively IL-4 dependent and IL-4 independent. The IgE potentiation cannot be explained by the inhibition of interferon-gamma (IFN-gamma) production since it is observed in the absence of endogenous secretion of IFN-gamma. HC inhibits the production of IgE-binding factors (soluble CD23) and the expression of the low-affinity receptor for IgE, also known as the (Fc epsilon RII) CD23 antigen; however, the residual expression of Fc epsilon RII by IL-4- and HC-treated peripheral blood mononuclear cells (PBMCs) is important since the IgE response of these cells is markedly inhibited by anti-CD23 monoclonal antibody. HC acts mainly by amplifying the cellular interactions between monocytes and lymphocytes; indeed, HC has no effect on monocyte-depleted PBMCs, and moreover, monocytes cannot be replaced by soluble factors. Most importantly, T cells are not required for the induction of IgE synthesis by costimulation with IL-4 and HC. However, the IgE response of rigorously T cell-depleted PBMCs may be further increased by the addition of T cells. Further analysis of the permissive effect of HC on the synthesis of IgE by T cell-depleted PBMCs suggests that HC acts in synergy with IL-4 to trigger the activation and the differentiation of B cells into IgE-producing cells.

Full text

PDF
872

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barbee R. A., Halonen M., Lebowitz M., Burrows B. Distribution of IgE in a community population sample: correlations with age, sex, and allergen skin test reactivity. J Allergy Clin Immunol. 1981 Aug;68(2):106–111. doi: 10.1016/0091-6749(81)90167-6. [DOI] [PubMed] [Google Scholar]
  2. Bargatze R. F., Katz D. H. "Allergic breakthrough" after antigen sensitization: height of IgE synthesis is temporally related to diurnal variation in endogenous steroid production. J Immunol. 1980 Nov;125(5):2306–2310. [PubMed] [Google Scholar]
  3. Cooper D. A., Duckett M., Petts V., Penny R. Corticosteroid enhancement of immunoglobulin synthesis by pokeweed mitogen-stimulated human lymphocytes. Clin Exp Immunol. 1979 Jul;37(1):145–151. [PMC free article] [PubMed] [Google Scholar]
  4. Cupps T. R., Fauci A. S. Corticosteroid-mediated immunoregulation in man. Immunol Rev. 1982;65:133–155. doi: 10.1111/j.1600-065x.1982.tb00431.x. [DOI] [PubMed] [Google Scholar]
  5. Cupps T. R., Gerrard T. L., Falkoff R. J., Whalen G., Fauci A. S. Effects of in vitro corticosteroids on B cell activation, proliferation, and differentiation. J Clin Invest. 1985 Feb;75(2):754–761. doi: 10.1172/JCI111757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Danon A., Assouline G. Inhibition of prostaglandin biosynthesis by corticosteroids requires RNA and protein synthesis. Nature. 1978 Jun 15;273(5663):552–554. doi: 10.1038/273552a0. [DOI] [PubMed] [Google Scholar]
  7. Daynes R. A., Araneo B. A. Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4. Eur J Immunol. 1989 Dec;19(12):2319–2325. doi: 10.1002/eji.1830191221. [DOI] [PubMed] [Google Scholar]
  8. DeKruyff R. H., Turner T., Abrams J. S., Palladino M. A., Jr, Umetsu D. T. Induction of human IgE synthesis by CD4+ T cell clones. Requirement for interleukin 4 and low molecular weight B cell growth factor. J Exp Med. 1989 Nov 1;170(5):1477–1493. doi: 10.1084/jem.170.5.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Del Prete G. F., Vercelli D., Tiri A., Maggi E., Rossi O., Romagnani S., Ricci M. Effect of in vitro irradiation and cell cycle-inhibitory drugs on the spontaneous human IgE synthesis in vitro. J Allergy Clin Immunol. 1987 Jan;79(1):69–77. doi: 10.1016/s0091-6749(87)80019-2. [DOI] [PubMed] [Google Scholar]
  10. Dupont E. Immunological actions of corticosteroids and cyclosporine A. Curr Opin Immunol. 1988 Dec;1(2):253–256. doi: 10.1016/0952-7915(88)90010-6. [DOI] [PubMed] [Google Scholar]
  11. Emilie D., Crevon M. C., Auffredou M. T., Galanaud P. Glucocorticosteroid-dependent synergy between interleukin 1 and interleukin 6 for human B lymphocyte differentiation. Eur J Immunol. 1988 Dec;18(12):2043–2047. doi: 10.1002/eji.1830181226. [DOI] [PubMed] [Google Scholar]
  12. Fauci A. S., Pratt K. R., Whalen G. Activation of human B lymphocytes. IV. Regulatory effects of corticosteroids on the triggering signal in the plaque-forming cell response of human peripheral blood B lymphocytes to polyclonal activation. J Immunol. 1977 Aug;119(2):598–603. [PubMed] [Google Scholar]
  13. Grayson J., Dooley N. J., Koski I. R., Blaese R. M. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes. J Clin Invest. 1981 Dec;68(6):1539–1547. doi: 10.1172/JCI110408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Guiochon-Mantel A., Loosfelt H., Ragot T., Bailly A., Atger M., Misrahi M., Perricaudet M., Milgrom E. Receptors bound to antiprogestin from abortive complexes with hormone responsive elements. Nature. 1988 Dec 15;336(6200):695–698. doi: 10.1038/336695a0. [DOI] [PubMed] [Google Scholar]
  15. Gunnar S., Johansson O., Juhlin L. Immunoglobulin E in "healed" atopic dermatitis and after treatment with corticosteroids and azathioprine. Br J Dermatol. 1970 Jan;82(1):10–13. doi: 10.1111/j.1365-2133.1970.tb02185.x. [DOI] [PubMed] [Google Scholar]
  16. Gustafsson J. A., Carlstedt-Duke J., Poellinger L., Okret S., Wikström A. C., Brönnegård M., Gillner M., Dong Y., Fuxe K., Cintra A. Biochemistry, molecular biology, and physiology of the glucocorticoid receptor. Endocr Rev. 1987 May;8(2):185–234. doi: 10.1210/edrv-8-2-185. [DOI] [PubMed] [Google Scholar]
  17. Hart P. H., Vitti G. F., Burgess D. R., Whitty G. A., Piccoli D. S., Hamilton J. A. Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. Proc Natl Acad Sci U S A. 1989 May;86(10):3803–3807. doi: 10.1073/pnas.86.10.3803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Henderson L. L., Larson J. B., Gleich G. J. Effect of corticosteroids on seasonal increases in IgE antibody. J Allergy Clin Immunol. 1973 Dec;52(6):352–357. doi: 10.1016/0091-6749(73)90094-8. [DOI] [PubMed] [Google Scholar]
  19. Jelinek D. F., Lipsky P. E. The roles of T cell factors in activation, cell cycle progression, and differentiation of human B cells. J Immunol. 1985 Mar;134(3):1690–1701. [PubMed] [Google Scholar]
  20. Maggi E., Del Prete G. F., Parronchi P., Tiri A., Macchia D., Biswas P., Simonelli C., Ricci M., Romagnani S. Role for T cells, IL-2 and IL-6 in the IL-4-dependent in vitro human IgE synthesis. Immunology. 1989 Nov;68(3):300–306. [PMC free article] [PubMed] [Google Scholar]
  21. Náray-Fejes-Tóth A., Cornwell G. G., Guyre P. M. Glucocorticoids inhibit IgE receptor expression on the human monocyte cell line U937. Immunology. 1985 Oct;56(2):359–366. [PMC free article] [PubMed] [Google Scholar]
  22. Orson F. M., Auzenne C. A. Glucocorticosteroid-induced immunoglobulin production requires intimate contact between B cells and monocytes. Cell Immunol. 1988 Mar;112(1):147–155. doi: 10.1016/0008-8749(88)90283-3. [DOI] [PubMed] [Google Scholar]
  23. Orson F. M., Flagge F. P., Cashaw J. L. T cell replacing factor for steroids (TRF-S): a 40,000 dalton protein produced by a T4+ T cell. J Immunol. 1986 Jul 15;137(2):578–584. [PubMed] [Google Scholar]
  24. Orson F. M., Grayson J., Pike S., De Seau V., Blaese R. M. T cell-replacing factor for glucocorticosteroid-induced immunoglobulin production. A unique steroid-dependent cytokine. J Exp Med. 1983 Nov 1;158(5):1473–1482. doi: 10.1084/jem.158.5.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peleman R., Wu J., Fargeas C., Delespesse G. Recombinant interleukin 4 suppresses the production of interferon gamma by human mononuclear cells. J Exp Med. 1989 Nov 1;170(5):1751–1756. doi: 10.1084/jem.170.5.1751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pène J., Chrétien I., Rousset F., Brière F., Bonnefoy J. Y., de Vries J. E. Modulation of IL-4-induced human IgE production in vitro by IFN-gamma and IL-5: the role of soluble CD23 (s-CD23). J Cell Biochem. 1989 Mar;39(3):253–264. doi: 10.1002/jcb.240390305. [DOI] [PubMed] [Google Scholar]
  27. Pène J., Rousset F., Brière F., Chrétien I., Bonnefoy J. Y., Spits H., Yokota T., Arai N., Arai K., Banchereau J. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6880–6884. doi: 10.1073/pnas.85.18.6880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ray A., Hemady Z., Rocklin R. E. Glucocorticoid-induced enhancement of IgE synthesis. N Engl Reg Allergy Proc. 1987 Mar-Apr;8(2):81–84. doi: 10.2500/108854187778994400. [DOI] [PubMed] [Google Scholar]
  29. Rector E., Nakajima T., Rocha C., Duncan D., Lestourgeon D., Mitchell R. S., Fischer J., Sehon A. H., Delespesse G. Detection and characterization of monoclonal antibodies specific to IgE receptors on human lymphocytes by flow cytometry. Immunology. 1985 Jul;55(3):481–488. [PMC free article] [PubMed] [Google Scholar]
  30. Rothman P., Lutzker S., Cook W., Coffman R., Alt F. W. Mitogen plus interleukin 4 induction of C epsilon transcripts in B lymphoid cells. J Exp Med. 1988 Dec 1;168(6):2385–2389. doi: 10.1084/jem.168.6.2385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sarfati M., Delespesse G. Possible role of human lymphocyte receptor for IgE (CD23) or its soluble fragments in the in vitro synthesis of human IgE. J Immunol. 1988 Oct 1;141(7):2195–2199. [PubMed] [Google Scholar]
  32. Sarfati M., Luo H., Delespesse G. IgE synthesis by chronic lymphocytic leukemia cells. J Exp Med. 1989 Nov 1;170(5):1775–1780. doi: 10.1084/jem.170.5.1775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sarfati M., Nutman T., Fonteyn C., Delespesse G. Presence of antigenic determinants common to Fc IgE receptors on human macrophages, T and B lymphocytes and IgE-binding factors. Immunology. 1986 Dec;59(4):569–575. [PMC free article] [PubMed] [Google Scholar]
  34. Sarfati M., Rector E., Rubio-Trujillo M., Wong K., Sehon A. H., Delespesse G. In vitro synthesis of IgE by human lymphocytes. III. IgE-potentiating activity of culture supernatants from Epstein-Barr virus (EBV) transformed B cells. Immunology. 1984 Oct;53(2):207–214. [PMC free article] [PubMed] [Google Scholar]
  35. Sarfati M., Rector E., Wong K., Rubio-Trujillo M., Sehon A. H., Delespesse G. In vitro synthesis of IgE by human lymphocytes. II. Enhancement of the spontaneous IgE synthesis by IgE-binding factors secreted by RPMI 8866 lymphoblastoid B cells. Immunology. 1984 Oct;53(2):197–205. [PMC free article] [PubMed] [Google Scholar]
  36. Settipane G. A., Pudupakkam R. K., McGowan J. H. Corticosteroid effect on immunoglobulins. J Allergy Clin Immunol. 1978 Sep;62(3):162–166. doi: 10.1016/0091-6749(78)90101-x. [DOI] [PubMed] [Google Scholar]
  37. Smeland E. B., Blomhoff H. K., Funderud S., Shalaby M. R., Espevik T. Interleukin 4 induces selective production of interleukin 6 from normal human B lymphocytes. J Exp Med. 1989 Oct 1;170(4):1463–1468. doi: 10.1084/jem.170.4.1463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Szczeklik A., Sladek K., Szczerba A., Dropinski J. Serum immunoglobulin E response to myocardial infarction. Circulation. 1988 Jun;77(6):1245–1249. doi: 10.1161/01.cir.77.6.1245. [DOI] [PubMed] [Google Scholar]
  39. Thiele D. L., Lipsky P. E. Modulation of human natural killer cell function by L-leucine methyl ester: monocyte-dependent depletion from human peripheral blood mononuclear cells. J Immunol. 1985 Feb;134(2):786–793. [PubMed] [Google Scholar]
  40. Thyphronitis G., Tsokos G. C., June C. H., Levine A. D., Finkelman F. D. IgE secretion by Epstein-Barr virus-infected purified human B lymphocytes is stimulated by interleukin 4 and suppressed by interferon gamma. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5580–5584. doi: 10.1073/pnas.86.14.5580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vercelli D., Jabara H. H., Arai K., Geha R. S. Induction of human IgE synthesis requires interleukin 4 and T/B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens. J Exp Med. 1989 Apr 1;169(4):1295–1307. doi: 10.1084/jem.169.4.1295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vercelli D., Jabara H. H., Arai K., Yokota T., Geha R. S. Endogenous interleukin 6 plays an obligatory role in interleukin 4-dependent human IgE synthesis. Eur J Immunol. 1989 Aug;19(8):1419–1424. doi: 10.1002/eji.1830190811. [DOI] [PubMed] [Google Scholar]
  43. Wira C. R., Sandoe C. P., Steele M. G. Glucocorticoid regulation of the humoral immune system. I. In vivo effects of dexamethasone on IgA and IgG in serum and at mucosal surfaces. J Immunol. 1990 Jan 1;144(1):142–146. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES