Intestinal Helminthic Infection Increases Serum Levels of IL-2 and Decreases Serum TGF-Beta Levels in Nigerian Asthmatic Patients

Abstract

Background: Asthma is less common in countries outside the organization for economic cooperation and development (OECD). One suggested mechanism for this disparity is the early life exposure to helminthic infection in non-OECD countries due to predominant Th1 immune response, which down-regulates Th2 responses required for exacerbation of asthma. This report is the first in the literature to describe the effects of helminthic infection on immune responses in asthmatic children compared to non-asthmatic controls. Methods: We administered the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire to 1690 high school students in three rural communities in southwestern Nigeria. Based on questionnaire responses and medical examination, identified asthma cases were matched with controls. Stool samples were collected from all subjects and screened for intestinal helminthic infection. The serum of 12 asthmatics and 12 non-asthmatics (6 with intestinal helminthic infection and 6 without intestinal helminthic infection in each group) were assayed for interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17A, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte macrophage colo- ny-stimulating factor (GM-CSF), and transforming growth factor-beta (TGF-β). Results: The mean (±SD) serum levels of IL-2 significantly increased in asthma cases with intestinal helminthic infection compared with asthma cases without infection (41.5 ± 9.7 vs. 29.7 ± 10.3; p = 0.035), controls with intestinal helminthic infection compared with cases without infection (52 ± 4.7 vs. 29.7 ± 10.3; p < 0.001), and controls with intestinal helminthic infection compared to controls without infection (52 ± 4.7 vs. 34.2 ± 10.4; p = 0.003). Mean levels of TGF-β significantly increased in controls without infection compared with asthma cases with infection (1833 ± 93.1 vs. 633.3 ± 294.4; p < 0.001), controls without intestinal helminthic infection compared with asthma cases without infection (1833 ± 93.1 vs. 916.7 ± 204.1; p < 0.001), controls with intestinal helminthic infection compared to controls without infection (2366.7 ± 760.7 vs. 1833 ± 93.1; p < 0.001), and controls with intestinal helminthic infection compared with asthma cases without infection (2366.7 ± 760.7 vs.916.71 ± 204.1; p = 0.007). Conclusion: Intestinal helminthic infection independently increases IL-2 levels, while asthma decreases the level of TGF-β, which is further depressed by intestinal helminthic infection.

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Arinola, G. , Oluwole, O. , Oladokun, R. , Adedokun, B. , Olopade, O. and Olopade, C. (2014) Intestinal Helminthic Infection Increases Serum Levels of IL-2 and Decreases Serum TGF-Beta Levels in Nigerian Asthmatic Patients. Open Journal of Immunology, 4, 1-8. doi: 10.4236/oji.2014.41001.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Asher, M.I., Montefort, S., Bjorksten, B., Lai, C.K., Strachan, D.P., Weiland, S.K., et al. (2006) Worldwide Time Trends in the Prevalence of Symptoms of Asthma, Allergic Rhinoconjunctivitis, and Eczema in Childhood: ISAAC Phases One and Three repeat Multicountry Cross-Sectional Surveys. Lancet, 368, 733-743. http://dx.doi.org/10.1016/S0140-6736(06)69283-0
[2] Weinberg, E.G. (2000) Urbanization and Childhood Asthma: An African Perspective. Journal of Allergy and Clinical Immunology, 105, 224-231. http://dx.doi.org/10.1016/S0091-6749(00)90069-1
[3] Yazdanbakhsh, M. and Matricardi, P.M. (2004) Parasites and the Hygiene Hypothesis: Regulating the Immune System? Clinical Review in Allergy and Immunology, 26, 15-24. http://dx.doi.org/10.1385/CRIAI:26:1:15
[4] Danilowicz-Luebert, E., O’Regan, N.L., Steinfelder, S. and Hartmann, S. (2011) Modulation of Specific and Allergy-Related Immune Responses by Helminths. Journal of Biomedicine and Biotechnology, 2011, Article ID: 821578. http://dx.doi.org/10.1155/2011/821578
[5] Flohr, C., Tuyen, L.N., Quinnell, R.J., Lewis, S., Minh, T.T., Campbell, J., et al. (2010) Reduced Helminth Burden Increases Allergen Skin Sensitization But Not Clinical Allergy: A Randomized, Double-Blind, Placebo-Controlled Trial in Vietnam. Clinical and Experimental Allergy, 40, 131-142.
[6] Cooper, P.J. (2002) Can Intestinal Helminth Infections (Geohelminths) Affect the Development and Expression of Asthma and allergic Disease? Clinical and Experimental Immunology, 128, 398-404. http://dx.doi.org/10.1046/j.1365-2249.2002.01908.x
[7] Holt, P.G., Macaubas, C., Stumbles, P.A. and Sly, P.D. (1999) The Role of Allergy in the Development of Asthma. Nature, 402, B12-B17. http://dx.doi.org/10.1038/35037009
[8] Barnes, P.J. (2008) The Cytokine Network in Asthma and Chronic Obstrcutive Pulmonary Disease. Journal of Clinical Investigation, 118, 3546-3556. http://dx.doi.org/10.1172/JCI36130
[9] Chung, K.F. and Barnes, P.J. (1999) Cytokines in Asthma. Thorax, 54, 825-857. http://dx.doi.org/10.1136/thx.54.9.825
[10] Araujo, M.I., Lopes, A.A., Medeiros, M., Cruz, A.A., Sousa-Atta, L. and Sole, D., et al. (2000) Inverse Association between Skin Response to Aeroallergens and Schistosoma mansoni Infection. International Archives of Allergy and Immunology, 123, 145-148. http://dx.doi.org/10.1159/000024433
[11] Cooper, P.J. (2004) The Potential Impact of Early Exposures to Geohelminth Infections on the Development of Atopy. Clinical Review in Allergy and Immunology, 26, 5-14. http://dx.doi.org/10.1385/CRIAI:26:1:5
[12] Wills-Karp, M., Santeliz, J. and Karp, C.L. (2001) The Germless Theory of Allergic Disease: Revisiting the Hygiene Hypothesis. Nature Review Immunology, 1, 69-75. http://dx.doi.org/10.1038/35095579
[13] Yazdanbakhsh, M., Kremsner, P.G. and van Ree, R. (2002) Allergy, Parasites, and the Hygiene Hypothesis. Science, 296, 490. http://dx.doi.org/10.1126/science.296.5567.490
[14] Hasan, M.M., Gofin, R. and Bar-Yishay, E. (2000) Urbanization and the Risk of Asthma among Schoolchildren in the Palestinian Authority. Journal of Asthma, 37, 353-360. http://dx.doi.org/10.3109/02770900009055459
[15] Maia, J.G., Marcopito, L.F., Amaral, A.N., Tavares Bde, F. and Santos, F.A. (2004) [Prevalence of Asthma and Asthma Symptoms among 13 and 14-Year-Old Schoolchildren, Brazil]. Revista de Saúde Pública, 38, 292-299. http://dx.doi.org/10.1590/S0034-89102004000200020
[16] van den Biggelaar, A.H., van Ree, R., Rodrigues, L.C., Lell, B., Deelder, A.M. and Kremsner, P.G., et al. (2000) Decreased Atopy in Children Infected with Schistosoma Haematobium: A Role for Parasite-Induced Interleukin-10. Lancet, 356, 1723-1727. http://dx.doi.org/10.1016/S0140-6736(00)03206-2
[17] Allen, J.E. and Wynn, T.A. (2011) Evolution of Th2 Immunity: A Rapid Repair Response to Tissue Destructive Pathogens. PLoS Pathogens, 6, Article ID: e1002003. http://dx.doi.org/10.1371/journal.ppat.1002003
[18] Girgis, N.M., Gundra, M.U. and Loke, O. (2013) Immune Regulation during Helminth Infections. PLoS Pathogens, 9, Article ID: 1003250.
[19] Oluwole, O., Arinola, G.O., Falade, A.G., Ige, O.M., Falusi, A.G., Huo, D., et al. (2013) Allergy Sensitization and Asthma among 13-and 14-Year Old Schoolchildren in Southwestern Nigeria. African Health Sciences, 13, 144-153.
[20] Ngoc, P.L., Gold, D.R., Tzianabos, A.O., Weiss, S.T. and Celedon, J.C. (2005) Cytokines, Allergy, and Asthma. Current Opinion in Allergy and Clinical Immunology, 5, 161-166. http://dx.doi.org/10.1097/01.all.0000162309.97480.45
[21] Romagnani, S. (2004) Immunologic Influences on Allergy and the TH1/TH2 Balance. Journal of Allergy and Clinical Immunology, 113, 395-400. http://dx.doi.org/10.1016/j.jaci.2003.11.025
[22] Barnes, P.J. (2002) Th2 Cytokines and Asthma: An Introduction. Respiratory Research, 2, 64-65. http://dx.doi.org/10.1186/rr39
[23] Bach, J.F. (2002) The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases. New England Journal of Medicine, 347, 911-920. http://dx.doi.org/10.1056/NEJMra020100
[24] Dillon, S.R., Sprecher, C., Hammond, A., Bilsborough, J., Rosenfeld-Franklin, M., Presnell, S.R., et al. (2004) Interleukin 31, a Cytokine Produced by Activated T Cells, Induces Dermatitis in Mice. Nature Immunology, 5, 752-760. http://dx.doi.org/10.1038/ni1084
[25] Finkelman, F.D., Shea-Donohue, T., Morris, S.C., Gildea, L., Strait, R., Madden, K.B., et al. (2004) Interleukin-4-and Interleukin-13-Mediated Host Protection against Intestinal Nematode Parasites. Immunology Review, 201, 139-155. http://dx.doi.org/10.1111/j.0105-2896.2004.00192.x
[26] Fort, M.M., Cheung, J., Yen, D., Li, J., Zurawski, S.M., Lo, S., et al. (2001) IL-25 induces IL-4, IL-5, and IL-13 and Th2-Associated Pathologies in Vivo. Immunity, 15, 985-995. http://dx.doi.org/10.1016/S1074-7613(01)00243-6
[27] Harnett, W. and Harnett, M.M. (2006) Molecular Basis of Worm-Induced Immunomodulation. Parasite Immunology, 28, 535-543. http://dx.doi.org/10.1111/j.1365-3024.2006.00893.x
[28] Wang, L.J., Cao, Y. and Shi, H.N. (2008) Helminth Infections and Intestinal Inflammation. World Journal of Gastroenterology, 14, 5125-5132. http://dx.doi.org/10.3748/wjg.14.5125
[29] Barbu, A.E. and Pecht, I. (2005) Desensitization of Mast Cells’ Secretory Response to an Immuno-Receptor Stimulus. Immunology Letter, 100, 78-87. http://dx.doi.org/10.1016/j.imlet.2005.06.009
[30] Sancho-Serra Mdel, C., Simarro, M. and Castells, M. (2011) Rapid IgE Desensitization Is Antigen Specific and Impairs Early and Late Mast Cell Responses Targeting FcepsilonRI Internalization. European Journal of Immunology, 41, 1004-1013. http://dx.doi.org/10.1016/j.imlet.2005.06.009
[31] Akdis, M., Verhagen, J., Taylor, A., Karamloo, F., Karagiannidis, C., Crameri, R., et al. (2004) Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-Specific T Regulatory 1 and T Helper 2 Cells. Journal of Experimental Medicine, 199, 1567-1575. http://dx.doi.org/10.1084/jem.20032058
[32] Smits, H.H., Everts, B., Hartgers, F.C. and Yazdanbakhsh, M. (2010) Chronic Helminth Infections Protect against Allergic Diseases by Active Regulatory Processes. Current Allergy and Asthma Report, 10, 3-12. http://dx.doi.org/10.1007/s11882-009-0085-3

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