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. 1995 Sep;101(3):474–479. doi: 10.1111/j.1365-2249.1995.tb03137.x

Hydrocortisone enhances total IgE levels--but not the synthesis of allergen-specific IgE--in a monocyte-dependent manner.

B Bohle 1, M Willheim 1, K Baier 1, B Stadler 1, S Spitzauer 1, O Scheiner 1, D Kraft 1, C Ebner 1
PMCID: PMC1553237  PMID: 7664494

Abstract

Recently, hydrocortisone (HC), when combined with human IL-4, has been reported to increase IgE levels in supernatants (SN) of in vitro cultured leucocytes. In this study we investigated the influence of HC on allergen-specific IgE synthesis. Moreover, we examined the relevance of different cell types in this respect. Peripheral blood mononuclear cells (PBMC), T-cell depleted PBMC, CD14-depleted PBMC and highly purified B cells from 10 allergic (birch pollen and/or grass pollen) patients and five non-allergic individuals were investigated. The cells were incubated with HC and/or recombinant human IL-4 (rIL-4) for 8 days. A considerable increase of total IgE was observed in HC/rIL-4-stimulated cultures compared with rIL-4 alone, HC alone or non-stimulated cultures. We demonstrate that this effect depends on the presence of monocytes in in vitro cultures. These results were seen in every experiment, irrespective of healthy or atopic state of the blood donor. The increase of IgE could not be attributed to a rise of birch pollen-and/or grass pollen-specific IgE in patients allergic to these allergens, as shown by IgE-immunoblot. Radio-allergosorbent test (RAST) investigations of HC/rIL-4-stimulated cells cultures from allergic and non-allergic patients confirmed that HC/rIL-4-induced elevated IgE production was also not due to increased production of IgE, specific for important aero-allergens (pollens, house dust mite or animal dander). Therefore we conclude that newly synthesized IgE is not specific for allergens, but that sequential isotype switching in human B cells leads to increased polyclonal IgE production.

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Selected References

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  1. Banchereau J., de Paoli P., Vallé A., Garcia E., Rousset F. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science. 1991 Jan 4;251(4989):70–72. doi: 10.1126/science.1702555. [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. Clark E. A., Ledbetter J. A. How B and T cells talk to each other. Nature. 1994 Feb 3;367(6462):425–428. doi: 10.1038/367425a0. [DOI] [PubMed] [Google Scholar]
  4. Crimi E., Voltolini S., Gianiorio P., Orengo G., Troise C., Brusasco V., Crimi P., Negrini A. C. Effect of seasonal exposure to pollen on specific bronchial sensitivity in allergic patients. J Allergy Clin Immunol. 1990 Jun;85(6):1014–1019. doi: 10.1016/0091-6749(90)90045-6. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. Jabara H. H., Fu S. M., Geha R. S., Vercelli D. CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells. J Exp Med. 1990 Dec 1;172(6):1861–1864. doi: 10.1084/jem.172.6.1861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jabara H. H., Loh R., Ramesh N., Vercelli D., Geha R. S. Sequential switching from mu to epsilon via gamma 4 in human B cells stimulated with IL-4 and hydrocortisone. J Immunol. 1993 Nov 1;151(9):4528–4533. [PubMed] [Google Scholar]
  11. Jabara H. H., Vercelli D. Engagement of CD14 on monocytes inhibits the synthesis of human Igs, including IgE. J Immunol. 1994 Aug 1;153(3):972–978. [PubMed] [Google Scholar]
  12. Jarolim E., Rumpold H., Endler A. T., Ebner H., Breitenbach M., Scheiner O., Kraft D. IgE and IgG antibodies of patients with allergy to birch pollen as tools to define the allergen profile of Betula verrucosa. Allergy. 1989 Aug;44(6):385–395. doi: 10.1111/j.1398-9995.1989.tb04169.x. [DOI] [PubMed] [Google Scholar]
  13. Kamoun M., Martin P. J., Hansen J. A., Brown M. A., Siadak A. W., Nowinski R. C. Identification of a human T lymphocyte surface protein associated with the E-rosette receptor. J Exp Med. 1981 Jan 1;153(1):207–212. doi: 10.1084/jem.153.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kerrebijn K. F., van Essen-Zandvliet E. E., Neijens H. J. Effect of long-term treatment with inhaled corticosteroids and beta-agonists on the bronchial responsiveness in children with asthma. J Allergy Clin Immunol. 1987 Apr;79(4):653–659. doi: 10.1016/s0091-6749(87)80163-x. [DOI] [PubMed] [Google Scholar]
  15. Klebl F. H., Weber G., Kalden J. R., Nüsslein H. G. In vitro and in vivo effect of glucocorticoids on IgE and IgG subclass secretion. Clin Exp Allergy. 1994 Nov;24(11):1022–1029. doi: 10.1111/j.1365-2222.1994.tb02738.x. [DOI] [PubMed] [Google Scholar]
  16. Kraan J., Koëter G. H., vd Mark T. W., Sluiter H. J., de Vries K. Changes in bronchial hyperreactivity induced by 4 weeks of treatment with antiasthmatic drugs in patients with allergic asthma: a comparison between budesonide and terbutaline. J Allergy Clin Immunol. 1985 Oct;76(4):628–636. doi: 10.1016/0091-6749(85)90786-9. [DOI] [PubMed] [Google Scholar]
  17. Miltenyi S., Müller W., Weichel W., Radbruch A. High gradient magnetic cell separation with MACS. Cytometry. 1990;11(2):231–238. doi: 10.1002/cyto.990110203. [DOI] [PubMed] [Google Scholar]
  18. Mosmann T. R., Coffman R. L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173. doi: 10.1146/annurev.iy.07.040189.001045. [DOI] [PubMed] [Google Scholar]
  19. Naclerio R. M., Adkinson N. F., Jr, Creticos P. S., Baroody F. M., Hamilton R. G., Norman P. S. Intranasal steroids inhibit seasonal increases in ragweed-specific immunoglobulin E antibodies. J Allergy Clin Immunol. 1993 Nov;92(5):717–721. doi: 10.1016/0091-6749(93)90015-8. [DOI] [PubMed] [Google Scholar]
  20. Nüsslein H. G., Träg T., Winter M., Dietz A., Kalden J. R. The role of T cells and the effect of hydrocortisone on interleukin-4-induced IgE synthesis by non-T cells. Clin Exp Immunol. 1992 Nov;90(2):286–292. doi: 10.1111/j.1365-2249.1992.tb07944.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nüsslein H. G., Weber G., Kalden J. R. Synthetic glucocorticoids potentiate IgE synthesis. Influence of steroid and nonsteroid hormones on human in vitro IgE secretion. Allergy. 1994 May;49(5):365–370. doi: 10.1111/j.1398-9995.1994.tb02283.x. [DOI] [PubMed] [Google Scholar]
  22. Sanderson R. J., Shepperdson R. T., Vatter A. E., Talmage D. W. Isolation and enumeration of peripheral blood monocytes. J Immunol. 1977 Apr;118(4):1409–1414. [PubMed] [Google Scholar]
  23. Schwartz R. H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell. 1992 Dec 24;71(7):1065–1068. doi: 10.1016/s0092-8674(05)80055-8. [DOI] [PubMed] [Google Scholar]
  24. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Shapira S. K., Vercelli D., Jabara H. H., Fu S. M., Geha R. S. Molecular analysis of the induction of immunoglobulin E synthesis in human B cells by interleukin 4 and engagement of CD40 antigen. J Exp Med. 1992 Jan 1;175(1):289–292. doi: 10.1084/jem.175.1.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Spriggs M. K., Armitage R. J., Strockbine L., Clifford K. N., Macduff B. M., Sato T. A., Maliszewski C. R., Fanslow W. C. Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. J Exp Med. 1992 Dec 1;176(6):1543–1550. doi: 10.1084/jem.176.6.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stevenson H. C. Isolation of human mononuclear leukocyte subsets by countercurrent centrifugal elutriation. Methods Enzymol. 1984;108:242–249. doi: 10.1016/s0076-6879(84)08087-3. [DOI] [PubMed] [Google Scholar]
  29. Valenta R., Vrtala S., Ebner C., Kraft D., Scheiner O. Diagnosis of grass pollen allergy with recombinant timothy grass (Phleum pratense) pollen allergens. Int Arch Allergy Immunol. 1992;97(4):287–294. doi: 10.1159/000236135. [DOI] [PubMed] [Google Scholar]
  30. Van Seventer G. A., Shimizu Y., Horgan K. J., Shaw S. The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells. J Immunol. 1990 Jun 15;144(12):4579–4586. [PubMed] [Google Scholar]
  31. Vercelli D., Geha R. S. Regulation of IgE synthesis in humans: a tale of two signals. J Allergy Clin Immunol. 1991 Sep;88(3 Pt 1):285–295. doi: 10.1016/0091-6749(91)90087-5. [DOI] [PubMed] [Google Scholar]
  32. Willheim M., Gessl A., Berger R., Schedle A., Luger T., Föster O., Boltz-Nitulescu G. IL-6 augments Fc IgE receptor (Fc epsilon RII/CD23) expression on human monoblastic/monocytic cell lines U937, THP-1, and Mono-Mac-6 but not on blood monocytes. Regulatory effects of IL-4 and IFN-gamma. J Immunol. 1991 Sep 15;147(6):1837–1842. [PubMed] [Google Scholar]
  33. Wu C. Y., Sarfati M., Heusser C., Fournier S., Rubio-Trujillo M., Peleman R., Delespesse G. Glucocorticoids increase the synthesis of immunoglobulin E by interleukin 4-stimulated human lymphocytes. J Clin Invest. 1991 Mar;87(3):870–877. doi: 10.1172/JCI115092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zieg G., Lack G., Harbeck R. J., Gelfand E. W., Leung D. Y. In vivo effects of glucocorticoids on IgE production. J Allergy Clin Immunol. 1994 Aug;94(2 Pt 1):222–230. doi: 10.1016/0091-6749(94)90044-2. [DOI] [PubMed] [Google Scholar]

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