Objectives: Interpretation of laboratory immune data in healthy human subjects is often challenging due to wide inter-subject variability. Since endocrine and immune mediators have been mutually interlinked, a potential explanation for the significant variability seen in immune data even when controlled for technical variability and demographics is differences in the binding affinity of ligand with hormone receptors on the surface of immune cells, which can be associated with single nucleotide polymorphisms (SNP). Methods: We categorized immunoregulatory cellular profiles from PBMC of 207 healthy volunteers according to glucocorticoid receptor (GR: Bcl1, TthIIII, and A3669G) and β2-adrenergic receptor (β2AR: Gly16Arg and Gln27Glu) polymorphisms. Subjects were genotyped for each SNP, and Th1, Th2, Th1/Th2 ratio, regulatory T cell (Treg), Tr1, and Th3 cell numbers were assessed. Immune parameters in the SNP groups were compared to the wild type (WT). Results: Significant differences were observed in Th2 and the Th1/Th2 ratio for the β2AR SNP Gly16Arg. Th1, the Th1/Th2 ratio, and Tr1 differed significantly by SNP of Gln27Glu. In addition, the effect of age on Th2 and the effect of the body mass index on the Th1/Th2 ratio significantly differed across subtypes of the Gly16Arg SNP. Significant differences based on allergic status and gender were also seen for Treg, Th1, and Th2 across Gly16Arg, Gln27Glu, and TthIIII SNP. Conclusions: These data suggest that SNP from various components of the stress-immune network may be useful for subgrouping of immune responses to more accurately categorize psychoneuroimmunological components of stress risk in individual subjects. This approach may have significant research and clinical potential.

1.
Irwin MR: Human psychoneuroimmunology: 20 years of discovery. Brain Behav Immun 2008;2:129–139.
2.
Zen M, Canova M, Campana C, Bettio S, Nalotto L, Rampudda M, Ramonda R, Iaccarino L, Doria A: The kaleidoscope of glucorticoid effects on immune system. Autoimmun Rev 2011;10:305–310.
3.
Butts CL, Jones YL, Lim JK, Salter CE, Belyavskaya E, Sternberg EM: Tissue expression of steroid hormone receptors is associated with differential immune responsiveness. Brain Behav Immun 2010;25:1000–1007.
4.
Wust S, Van Rossum EF, Federenko IS, Koper JW, Kumsta R, Hellhammer DH: Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress. J Clin Endocrinol Metab 2004;89:565–573.
5.
Pedersen A, Zachariae R, Bovbjerg DH: Influence of psychological stress on upper respiratory infection: a meta-analysis of prospective studies. Psychosom Med 2010;72:823–832.
6.
Oh YM, Kim YS, Yoo SH, Kim SK, Kim DS: Association between stress and asthma symptoms: a population-based study. Respirology 2004;9:363–368.
7.
Stojanovich L: Stress and autoimmunity. Autoimmun Rev 2010;9:A271–A276.
8.
Tas F, Karalar U, Aliustaoglu M, Keskin S, Can G, Cinar FE: The major stressful life events and cancer: stress history and cancer. Med Oncol 2011, E-pub ahead of print, DOI 10.1007/s12032-011-9927-7.
9.
Agarwal SK, Marshall GD: Glucocorticoid-induced type 1/type 2 cytokine alterations in humans: a model for stress-related immune dysfunction. J Interferon Cytokine Res 1998;18:1059–1068.
10.
Salicru AN, Sams CF, Marshall GD: Cooperative effects of corticosteroids and catecholamines upon immune deviation of the type-1/type-2 cytokine balance in favor of type-2 expression in human peripheral blood mononuclear cells. Brain Behav Immun 2007;21:913–920.
11.
Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, Carr VA, Robinson DS: Relation of CD4+CD25+ regulatory T cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 2004;363:608–615.
12.
Farrell AM, Antrobus P, Simpson D, Powell S, Chapel HM, Ferry BL: A rapid flow cytometric assay to detect CD4+ and CD8+ T-helper (Th) 0, Th1 and Th2 cells in whole blood and its application to study cytokine levels in atopic dermatitis before and after cyclosporin therapy. Br J Dermatol 2001;144:24–33.
13.
Hawkins GA, Tantisira K, Meyers DA, Ampleford EJ, Moore WC, Klanderman B, Liggett SB, Peters SP, Weiss ST, Bleeker ER: Sequence, haplotype, and association analysis of ADRbeta2 in a multiethnic asthma case-control study. Am J Respir Crit Care Med 2006;174:1101–1109.
14.
Thakkinstian A, McEvoy M, Minelli C, Gibson P, Hancox B, Duffy D, Thompson J, Hall I, Kaufman J, Leung TF, Helms PJ, Hakonarson H, Halpi E, Navon R, Attia J: Systematic review and meta-analysis of the association between beta-2-adrenoceptor polymorphisms and asthma: a HuGE review. Am J Epidemiol 2005;162:201–211.
15.
Cho SH: Pharmacogenomic approaches to asthma treatment. Allergy Asthma Immunol Res 2010;2:177–182.
16.
Eriksson J, Ekerljung L, Pulleritis T, Holmberg K, Ronmark E, Lotvall J, Lundback B: Prevalence of chronic nasal symptoms in West Sweden: risk factors and relation to self-reported allergic rhinitis and lower respiratory symptoms. Int Arch Allergy Immunol 2011;154:155–163.
17.
Xiang L, Del Ben KS, Rehm KE, Marshall GD Jr: Effects of acute stress-induced immunomodulation on Th1/Th2 cytokine and catecholamine receptor expression in human peripheral blood cells. Neuropsychobiology 2012;65:12–19.
18.
Marshall GD, Agarwal SK, Lloyd C, Cohen L, Henninger EM, Morris GJ: Cytokine dysregulation associated with exam stress in healthy medical students. Brain Behav Immun 1998;12:297–307.
19.
Reboradosa C, Kogevinas M, Guerra S, Castro-Giner F, Jarvis D, Cazzoletti L, Pin I, Siroux V, Wjst M, Antò JM, de Marco R, Estivill X, Corsico AG, Nielson R, Janson C: ADRB2 Gly16Arg polymorphism, asthma control and lung function decline. Eur Respir J 2011;38:1029–1035.
20.
Gupta S, Awasthi S: Pharmacogenomics of pediatric asthma. Indian J Hum Genet 2010;16:111–118.
21.
Iwamoto Y, Ohishi M, Yuan M, Tatara Y, Kato N, Takeya Y, Onishi M, Maekawa Y, Kamide K, Rakugi H: β-Adrenergic receptor gene polymorphism is a genetic risk factor for cardiovascular disease: a cohort study with hypertensive patients. Hypertens Res 2011;34:573–577.
22.
Kostik MM, Klyushina AA, Moskalenko MV, Scheplyagina LA, Larionova VI: Glucocorticoid receptor gene polymorphisms and juvenile idiopathic arthritis. Pediatr Rheumatol Online J 2011;9:2.
23.
Decorti G, De Iudicibus S, Stocco G, Martelossi S, Drigo I, Bartoli F, Ventura A: Glucocorticoid receptor polymorphisms in inflammatory bowel disease. Gut 2006;55:1053–1054.
24.
Spijker AT, van Rossum EF: Glucocorticoid receptor polymorphisms in major depression. Focus on glucorticoid sensitivity and neurocognitive functioning. Ann NY Acad Sci 2009;1179:199–215.
25.
Spijker AT, Giltay EJ, van Rossum EF, Manenschijn L, Derijk RH, Haffmans J, Zitman FG, Hoencamp E: Glucocorticoid and mineralocorticoid receptor polymorphisms and clinical characteristics in bipolar disorder. Psychoneuroendocrinology 2011;36:1460–1469.
26.
Lima JJ, Blake KV, Tantisira KG, Weiss ST: Pharmacogenetics of asthma. Curr Opin Pulm Med 2009;15:57–62.
27.
Gibson PG, McDonald VM, Marks GB: Asthma in older adults. Lancet 2010;376:803–813.
28.
Beuther DA: Obesity and asthma. Clin Chest Med 2009;30:479–488, viii.
29.
Lugogo NL, Kraft M, Dixon AE: Does obesity produce a distinct asthma phenotype? J Appl Physiol 2010;108:729–734.
30.
Pelta Fernandez R, De Miguel Diez J, Alvarez-Perea A, Magan Tapia P, Jimenez Garcia R, Sanz De Burgoa Gomez-Pinan V: Risk factors for asthma onset between the ages of 12 and 40. Results of the FENASMA Study (in Spanish). Arch Bronconeumol 2011;47:433–440.
31.
Lee JH, Yu HH, Wang LC, Yang YH, Lin YT, Chiang BL: The levels of CD4+CD25+ regulatory T cells in paediatric patients with allergic rhinitis and bronchial asthma. Clin Exp Immunol 2007;148:53–63.
32.
Bellinghausen I, Klostermann B, Knop J, Saloga J: Human CD4+CD25+ cells derived from the majority of atopic donors are able to suppress Th1 and Th2 cytokine production. J Allergy Clin Immunol 2003;11:862–868.
33.
Grindebacke H, Wing K, Andersson AC, Suri-Payer E, Rak S, Rudin A: Defective suppression of Th2 cytokines by CD4CD25 regulatory T cells in birch allergics during birch pollen season. Clin Exp Allergy 2004;34:1364–1372.
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.