Analytical study of inflammatory cytokines and immunoglobulin expression following dust mite allergen exposure in pregnant mice

  • Risa Etika Department of Pediatrics, Airlangga University
  • Subijanto Marto Sudarmo Department of Pediatrics, Faculty of Medicine, Universitas Airlangga
  • Suwarno Suwarno Faculty of Veterinary, Universitas Airlangga
  • Muhammad Pradhika Mapindra Department of Pediatrics, Faculty of Medicine, Universitas Airlangga
  • Muhammad Pradhiki Mahindra Department of Pediatrics, Faculty of Medicine, Universitas Airlangga
Keywords: mite allergen; pregnant BALB/C mice; newborn mice; tolerance; cytokine


Background Allergen tolerability due to allergic immune reactions could be transferred through the placenta from maternal to fetal circulation. Hence, a further investigation regarding the tolerability following mite allergen exposures is desirable.

Objective  To evaluate various doses of mite allergens and cytokines associated with Th1, Th2, and Treg cells with regards to possible allergic tolerance in neonatal mice.

Methods This study used an experimental design with a post-test only control group, to assess the effect of mite allergens on pregnant BALB/C mice and their newborns. In this study female BALB/C mice aged 10 weeks were mated with male mice, then pregnant BALB/C mice were exposed to allergens at 4 weeks gestation. During pregnancy, pregnant females’ blood specimens were taken to measure cytokines and immunoglobulins. Meanwhile, neonatal blood specimens were taken at 2 weeks postnatally to measure cytokines and immunoglobulins. Blood specimens from pregnant BALB/C mice and their newborns were evaluated using ELISA kits for the following cytokines: interleukin (IL)-2, interferon (IFN)-γ, interleukin (IL)-4, IL-5, IL-10, TGF-β1, as well as immunoglobulins (Ig)G-1, IgG-2a, IgG-2b, IgG3 subclass, IgM, IgA, and IgE. The case group was the group that received high and low doses of exposure, while the control group did not get exposure.

Results In response to low dose mite allergen exposure, there were significant increases of IL-2, IFN-y, and IL-4, IL-5, and TGF-β1 in mothers and neonates. Pregnant mices that received high doses of allergens, however, had significant increases in IL-5 and TGF-B1; results were likewise for their offspring. Mothers and neonates, had significantly increased expression of IgG subclasses after a low dose of dust mite allergen. Following a ten-fold increase in allergen dose, the mothers showed significant increases in IgA, IgM, IgE, and IgG subclasses, whereas in neonatal mice, those immunoglobulin levels were not significantly different from control mice.

Conclusion  Exposure to mite allergens can trigger regulatory functions of Th1, Th2, and Tregs cells to activate their cytokines, except IL-10. The regulatory function of Tregs is dominated by TGFβ in maternal and neonatal mice, at low and high doses. Th1 cytokines express cytokines during exposure only to low-dose allergens and Th2 cells regulate IL-5 levels to both low- and high-dose allergens.


1. Platts-Mills TA, Erwin EA, Allison AB, Blumenthal K, Barr M, Sredl D, et al. The relevance of maternal immune responses to inhalant allergens to maternal symptoms, passive transfer to the infant, and development of antibodies in the first 2 years of life. J Allergy Clin Immunol. 2003;111:123-30. DOI: 10.1067/mai.2003.10.
2. Miller JD. The role of dust mites in allergy. Clinic Rev Allerg Immunol. 2019;57:329–312. DOI: 10.1007/s12016-018-8693-0.
3. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr. 2006;83:1256-64. DOI: 10.1093/ajcn/83.6.1256.
4. PrabhuDas M, Bonney E, Caron K, Dey S, Erlebacher A, Fazleabas A, et al. Immune mechanisms at the maternal-fetal interface: perspectives and challenges. Nat Immunol. 2015;16:328–34. DOI: 10.1038/ni.3131.
5. Pali-Schöll I, Renz H, Jensen-Jarolim E. Update on allergies in pregnancy, lactation, and early childhood. J Allergy Clin Immunol. 2009;123:1012–21. DOI: 10.1016/j.jaci.2009.01.045.
6. Jones CA, Holloway JA, Warner JO. Does atopic disease start in foetal life?. Allergy. 2000;55:10-2. DOI: 10.1034/j.1398-9995.2000.00109.x.
7. Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008;454:454–445. DOI: 10.1038/nature07204.
8. Akoh CC, Pressman EK, Cooper E, Queenan RA, Pillittere O’Brien KO. Low Vitamin D is Associated With Infections and Proinflammatory Cytokines During Pregnancy. Reprod. Sci. 2018;25:423–414. DOI: 10.1177/1933719117715124.
9. Garcia-Serna AM, Martin-Orozco E, Hernandez-Caselles T, Morales E. Prenatal and Perinatal Enviromental Influences Shaping the Neonatal Immune System: A Focus on Asthma and Allergy Origins. International Journal of Environmental Research and Public Health. 2021;18:3962. DOI: 10.3390/ijerph18083962.
10. Scott-Taylor TH, Axinia S, Amin S, Pettengell R. Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy. Immunity, Inflammation, and Disease. 2017;6:33-13. DOI: 10.1002/iid3.192.
11. Cook-Mills JM. Maternal influences over offspring allergic responses. Current allergy and asthma reports. 2015;15:501. DOI: 10.1007/s11882-014-0501-1.
12. Fouda GG, Martinez DR, Swamy GK, Permar SR. The Impact of IgG transplacental transfer on early life immunity. Immuno Horizons. 2018;2:25-14. DOI: 10.4049/immunohorizons.1700057.
13. Romagnani S. The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?. Immunology. 2004;112:363–352. DOI: 10.1111/j.1365-2567.2004.01925.x.
14. Robertson, S. A., Petroff, M. G., & Hunt, J. S. Immunology of pregnancy. Knobil and Neill’s Physiology of Reproduction. 2015;4:1874-1835. DOI: 10.1016/B978-0-12-397175-3.00041-7.
15. Diah K. Bersahabat Dengan Hewan Coba. Jogjakarta: Gajah Mada University Pers; 2004.
16. Giavina-Bianchi P, Kalil J, Rizzo LV. Development of an animal model for allergic conjunctivitis: influence of genetic factors and allergen concentration on immune response. Acta ophthalmologica. 2008;86:675–670. DOI: 10.1111/j.1600-0420.2007.01134.x.
17. Yoon HS. Neonatal Innate Immunity and Toll-like Receptor. Korean Journal of Pediatrics. 2010;53:988-985. DOI: 10.3345%2Fkjp.2010.53.12.985.
18. Cates EC, Fattouh R, Wattie J, Inman MD, Goncharova S, Coyle A J, et al. Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism. Journal of immunology (Baltimore, Md. : 1950). 2004;173:6392–6384. DOI: 10.4049/jimmunol.173.10.6384.
19. Gregory LG, Causton B, Murdoch JR, Mathie SA, O'Donnell V, Thomas CP, Priest FM, et al. Inhaled house dust mite induces pulmonary T helper 2 cytokine production. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2009;39:1610–1597. DOI: 10.1111/j.1365-2222.2009.03302.x.
20. Victor Jr JR, Fusaro AE, da Silva Duarte AJ, Sato MN. Preconception maternal immunization to dust mite inhibits the type I hypersensitivity response of offspring. Journal of allergy and clinical immunology. 2003;111:277-269. DOI: 10.1067/mai.2003.39.
21. Bener A, Ehlayel MS, Tulic MK, Hamid Q. Vitamin D deficiency as a strong predictor of asthma in children. International archives of allergy and immunology. 2012;157:175-168. DOI: 10.1159/000323941.
22. Wang H, Liu J, Zong Y, Xu Y, Deng W, Zhu H, et al. miR-106b aberrantly expressed in a double transgenic mouse model for Alzheimer's disease targets TGF-β type II receptor. Brain research. 2010;1357:174-166. DOI: 10.1016/j.brainres.2010.08.023.
23. Fattouh R, Al-Garawi A, Fattouh M, Arias K, Walker TD, Goncharova S, et al. Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite–induced airway disease. American journal of respiratory and critical care medicine. 2011;183:188-179. DOI: 10.1164/rccm.200905-0736OC.
24. Saglani S, Mathie SA, Gregory LG, Bell MJ, Bush A, Lloyd CM. Pathophysiological features of asthma develop in parallel in house dust mite–exposed neonatal mice. American journal of respiratory cell and molecular biology. 2009;41:289-281. DOI: 10.1165/rcmb.2008-0396OC.
How to Cite
Etika R, Sudarmo SM, Suwarno S, Mapindra MP, Mahindra MP. Analytical study of inflammatory cytokines and immunoglobulin expression following dust mite allergen exposure in pregnant mice. PI [Internet]. 22Nov.2021 [cited 20Jan.2022];61(6):336-2. Available from:
Pediatric Allergy Immunology
Received 2020-11-18
Accepted 2021-11-22
Published 2021-11-22