Background: Studies using rush immunotherapy (RIT) have shown that rapid protection can be achieved using protocols allowing a fast increment of allergen dose. We examined the early effects of RIT on basophil numbers and expression of CD203c, production of interleukin (IL)-4 and IL-13 and histamine release by basophils in the peripheral blood of patients treated with immunotherapy and controls. Methods: Twelve patients treated with RIT and 4 untreated controls were included in the study. Any adverse events were evaluated during the incremental phase of RIT. Mononuclear cells were isolated before the start of RIT and 3 days, 1 week, 4 weeks and 3 months after the beginning of the treatment. Histamine release upon allergen stimulation, expression of CD203c and allergen-induced production of IL-4 and IL-13 by basophils were examined. Results: Significant decreases in blood basophil count (p = 0.02) were observed early in the treatment, returning to baseline values 1 week after the start of RIT. Similarly, histamine release decreased at day 3 (p = 0.02), but returned to pretreatment levels after 1 week. Also, the percentage of IL-4+ and IL-13+ basophils and levels of CD203c expression were markedly reduced early in the treatment. IL-4 and IL-13 production correlated with histamine release and CD203c expression. Histamine release and production of IL-4 and IL-13 by basophils before the treatment correlated with the severity of adverse events during the incremental phase of RIT. Conclusion: We report the decrease in blood basophil numbers, their lower activation status and the reduced production of IL-4 and IL-13 early in the course of RIT. This early suppression of basophil activation could be one mechanism behind the protective effect of RIT.

Keywords:
Rush immunotherapy, Basophil activation, CD203c expression, Histamine release
1.
Van Metre TE Jr, Marsh DG, Adkinson NF Jr, Kagey-Sobotka A, Khattignavong A, Norman PS Jr, Rosenberg GL: Immunotherapy for cat asthma. J Allergy Clin Immunol 1988;82:1055–1068.
2.
Varney VA, Edwards J, Tabbah K, Brewster H, Mavroleon G, Frew AJ: Clinical efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial. Clin Exp Allergy 1997;27:860–867.
3.
Arvidsson MB, Lowhagen O, Rak S: Effect of 2-year placebo-controlled immunotherapy on airway symptoms and medication in patients with birch pollen allergy. J Allergy Clin Immunol 2002;109:777–783.
4.
Jutel M, Skrbic D, Pichler WJ, Müller UR: Ultra rush bee venom immunotherapy does not reduce cutaneous weal responses to bee venom and codeine phosphate. Clin Exp Allergy 1995;25:1205–1210.
5.
Jutel M, Muller UR, Fricker M, Rihs S, Pichler WJ, Dahinden C: Influence of bee venom immunotherapy on degranulation and leukotriene generation in human blood basophils. Clin Exp Allergy 1996;26:1112–1118.
6.
Brown MA, Hural J: Functions of IL-4 and control of its expression. Crit Rev Immunol 1997;17:1–32.
7.
Yanagihara Y, Kajiwara K, Basaki Y, Ikizawa K, Ebisawa M, Ra C, Tachimoto H, Saito H: Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation. Clin Exp Immunol 1998;111:136–143.
8.
Oda N, Yamashita N, Minoguchi K, Takeno M, Kaneko S, Sakane T, Adachi M: Long-term analysis of allergen-specific T cell clones from patients with asthma treated with allergen rush immunotherapy. Cell Immunol 1998;190:43–50.
9.
Akoum H, Tsicopoulos A, Vorng H, Wallaert B, Dessaint JP, Joseph M, Hamid Q, Tonnel AB: Venom immunotherapy modulates interleukin-4 and interferon-γ messenger RNA expression of peripheral T lymphocytes. Immunology 1996;87:593–598.
10.
Bellinghausen I, Metz G, Enk AH, Christmann S, Knop J, Saloga J: Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects. Eur J Immunol 1997;27:1131–1139.
11.
Pene J, Desroches A, Paradis L, Lebel B, Farce M, Nicodemus CF, Yssel H, Bousquet J: Immunotherapy with Fel d 1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. J Allergy Clin Immunol 1998;102:571–578.
12.
Marcotte GV, Braun CM, Norman PS, Nicodemus CF, Kagey-Sobotka A, Lichtenstein LM, Essayan DM: Effects of peptide therapy on ex vivo T-cell responses. J Allergy Clin Immunol 1998;101:506–513.
13.
Ewbank PA, Murray J, Sanders K, Curran-Everett D, Dreskin S, Nelson HS: A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract. J Allergy Clin Immunol 2003;111:155–161.
14.
Devouassoux G, Foster B, Scott LM, Metcalfe DD, Prussin C: Frequency and characterization of antigen-specific IL-4- and IL-13-producing basophils and T cells in peripheral blood of healthy and asthmatic subjects. J Allergy Clin Immunol 1999;104:811–819.
15.
Gibbs BF, Haas H, Wolff HH, Grabbe J: Early IgE-dependent release of IL-4 and IL-13 from leukocytes is restricted to basophils: a comparison with other granulocytes and mononuclear cells. Inflamm Res 2000;49(suppl 1):S9–S10.
16.
Shimizu Y, Shichijo M, Hiramatsu K, Takeuchi M, Nagai H, Takagi K: Mite antigen-induced IL-4 and IL-13 production by basophils derived from atopic asthma patients. Clin Exp Allergy 1998;28:497–503.
17.
Platz IJ, Binder M, Marxer A, Lischka G, Valent P, Buhring HJ: Hymenoptera-venom-induced upregulation of the basophil activation marker ecto-nucleotide pyrophosphatase/phosphodiesterase 3 in sensitized individuals. Int Arch Allergy Immunol 2001;126:335–342.
18.
Charlesworth EN, Hood AF, Soter NA, Kagey-Sobotka A, Norman PS, Lichtenstein LM: Cutaneous late-phase response to allergen. Mediator release and inflammatory cell infiltration. J Clin Invest 1989;83:1519–1526.
19.
McHugh SM, Deighton J, Stewart AG, Lachmann PJ, Ewan PW: Bee venom immunotherapy induces a shift in cytokine responses from a TH-2 to a TH-1 dominant pattern: comparison of rush and conventional immunotherapy. Clin Exp Allergy 1995;25:828–838.
20.
Irani AM, Huang C, Xia HZ, Kepley C, Nafie A, Fouda ED, Craig S, Zweiman B, Schwartz LB: Immunohistochemical detection of human basophils in late-phase skin reactions. J Allergy Clin Immunol 1998;101:354–362.
21.
Pierkes M, Bellinghausen I, Hultsch T, Metz G, Knop J, Saloga J: Decreased release of histamine and sulfidoleukotrienes by human peripheral blood leukocytes after wasp venom immunotherapy is partially due to induction of IL-10 and IFN-γ production of T cells. J Allergy Clin Immunol 1999;103:326–332.
22.
Ying S, Meng Q, Barata LT, Robinson DS, Durham SR, Kay AB: Associations between IL-13 and IL-4 (mRNA and protein), vascular cell adhesion molecule-1 expression, and the infiltration of eosinophils, macrophages, and T cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Immunol 1997;158:5050–5057.
23.
Li L, Xia Y, Nguyen A, Lai YH, Feng L, Mosmann TR, Lo D: Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells. J Immunol 1999;162:2477–2487.
24.
Toru H, Ra C, Nonoyama S, Suzuki K, Yata J, Nakahata T: Induction of the high-affinity IgE receptor (FcεRI) on human mast cells by IL-4. Int Immunol 1996;8:1367–1373.
25.
Strait RT, Morris SC, Smiley K, Urban JF Jr, Finkelman FD: IL-4 exacerbates anaphylaxis. J Immunol 2003;170:3835–3842.
26.
Leonard C, Tormey V, Burke C, Poulter LW: Allergen-induced cytokine production in atopic disease and its relationship to disease severity. Am J Respir Cell Mol Biol 1997;17:368–375.
27.
Humbert M, Corrigan CJ, Kimmitt P, Till SJ, Kay AB, Durham SR: Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med 1997;156:704–708.
© 2006 S. Karger AG, Basel
2006
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.