Skip to main content
SpringerLink
Log in

Association of interleukin-18 and asthma

  • REVIEW
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Cytokine-mediated immunity plays a dominant role in the pathogenesis of various immune diseases, including asthma. The recent identification of the family interleukin (IL)-1-related cytokine IL-18 now contributes to our understanding of the fine-tuning of cellular immunity. IL-18 can act as a cofactor for Th2 cell development and IgE production and also plays an important role in the differentiation of Th1 cells. Recent work identified an IL-18 association with the pathogenesis of asthma, wherein increased IL-18 expression was found in the serum of patients. Furthermore, IL-18 polymorphisms with susceptibility to asthma were reported, suggesting that IL-18 may be therapeutically relevant to asthma. In this review, we discuss the role of IL-18 in the pathogenesis of asthma and its therapeutic potential based on current research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bousquet, J., P.J. Bousquet, P. Godard, and J.P. Daures. 2005. The public health implications of asthma. Bulletin of the World Health Organization 83: 548–554.

    PubMed  PubMed Central  Google Scholar 

  2. Deo, S.S., K.J. Mistry, A.M. Kakade, and P.V. Niphadkar. 2010. Role played by Th2 type cytokines in IgE mediated allergy and asthma. Lung India : Official Organ of Indian Chest Society 27: 66–71.

    Article  Google Scholar 

  3. Lund, S., H.H. Walford, and T.A. Doherty. 2013. Type 2 innate lymphoid cells in allergic disease. Current Immunology Reviews 9: 214–221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sims, J.E. 2002. IL-1 and IL-18 receptors, and their extended family. Current Opinion in Immunology 14: 117–122.

    Article  CAS  PubMed  Google Scholar 

  5. Okamura, H., H. Tsutsi, T. Komatsu, M. Yutsudo, A. Hakura, T. Tanimoto, et al. 1995. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378: 88–91.

    Article  CAS  PubMed  Google Scholar 

  6. Nakanishi, K., T. Yoshimoto, H. Tsutsui, and H. Okamura. 2001. Interleukin-18 regulates both Th1 and Th2 responses. Annual Review of Immunology 19: 423–474.

    Article  CAS  PubMed  Google Scholar 

  7. Romagnani, S. 1999. Th1/Th2 cells. Inflammatory Bowel Diseases 5: 285–294.

    Article  CAS  PubMed  Google Scholar 

  8. Wild, J.S., A. Sigounas, N. Sur, M.S. Siddiqui, R. Alam, M. Kurimoto, et al. 2000. IFN-gamma-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. Journal of Immunology 164: 2701–2710.

    Article  CAS  Google Scholar 

  9. Rovina, N., E. Dima, P. Bakakos, E. Tseliou, K. Kontogianni, S. Papiris, et al. 2015. Low interleukin (IL)-18 levels in sputum supernatants of patients with severe refractory asthma. Respiratory Medicine 109: 580–587.

    Article  PubMed  Google Scholar 

  10. Imaoka, H., G.M. Gauvreau, R.M. Watson, S.G. Smith, B. Dua, A.J. Baatjes, et al. 2011. Interleukin-18 and interleukin-18 receptor-alpha expression in allergic asthma. The European Respiratory Journal 38: 981–983.

    Article  CAS  PubMed  Google Scholar 

  11. Imaoka, H., S. Takenaka, T. Kawayama, H. Oda, Y. Kaku, M. Matsuoka, et al. 2013. Increased serum levels of soluble IL-18 receptor complex in patients with allergic asthma. Allergology International: Official Journal of the Japanese Society of Allergology 62: 513–515.

    Article  CAS  Google Scholar 

  12. Kawayama, T., M. Okamoto, H. Imaoka, S. Kato, H.A. Young, and T. Hoshino. 2012. Interleukin-18 in pulmonary inflammatory diseases. Journal of Interferon & Cytokine Research: the Official Journal of The International Society for Interferon and Cytokine Research 32: 443–449.

    Article  CAS  Google Scholar 

  13. Lu, H., X. Yang, K. Takeda, D. Zhang, Y. Fan, M. Luo, et al. 2000. Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity. Molecular Medicine 6: 604–612.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Mihm, S., S. Schweyer, and G. Ramadori. 2003. Expression of the chemokine IP-10 correlates with the accumulation of hepatic IFN-gamma and IL-18 mRNA in chronic hepatitis C but not in hepatitis B. Journal of Medical Virology 70: 562–570.

    Article  CAS  PubMed  Google Scholar 

  15. Mallat, Z., A. Corbaz, A. Scoazec, S. Besnard, G. Leseche, Y. Chvatchko, et al. 2001. Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability. Circulation 104: 1598–1603.

    Article  CAS  PubMed  Google Scholar 

  16. Guo, H., H. Deng, H. Cui, X. Peng, J. Fang, Z. Zuo, et al. 2015. Nickel chloride (NiCl2)-caused inflammatory responses via activation of NF-kappaB pathway and reduction of anti-inflammatory mediator expression in the kidney. Oncotarget 6: 28607–28620.

    PubMed  PubMed Central  Google Scholar 

  17. Debets, R., J.C. Timans, T. Churakowa, S. Zurawski, R. de Waal Malefyt, K.W. Moore, et al. 2000. IL-18 receptors, their role in ligand binding and function: anti-IL-1RAcPL antibody, a potent antagonist of IL-18. Journal of Immunology 165: 4950–4956.

    Article  CAS  Google Scholar 

  18. Harada, M., K. Obara, T. Hirota, T. Yoshimoto, Y. Hitomi, M. Sakashita, et al. 2009. A functional polymorphism in IL-18 is associated with severity of bronchial asthma. American Journal of Respiratory and Critical Care Medicine 180: 1048–1055.

    Article  CAS  PubMed  Google Scholar 

  19. Yang D.X., Li N., Zhang X.L., Wang Q. 2012. [Serum interleukin 18 and 33 levels and its clinical significance in asthma patients]. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases 35:493–496.

  20. Zhang, J., L. Zheng, D. Zhu, H. An, Y. Yang, Y. Liang, et al. 2014. Polymorphisms in the interleukin 18 receptor 1 gene and tuberculosis susceptibility among Chinese. PloS One 9: e110734.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kuribayashi, K., T. Kodama, H. Okamura, M. Sugita, and T. Matsuyama. 2002. Effects of post-inhalation treatment with interleukin-12 on airway hyper-reactivity, eosinophilia and interleukin-18 receptor expression in a mouse model of asthma. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology 32: 641–649.

    Article  CAS  Google Scholar 

  22. Lunding, L., A. Schroder, and M. Wegmann. 2015. Allergic airway inflammation: unravelling the relationship between IL-37, IL-18Ralpha and Tir8/SIGIRR. Expert Review of Respiratory Medicine 9: 739–750.

    Article  CAS  PubMed  Google Scholar 

  23. Hossny, E.M., S.S. El-Sayed, E.S. El-Hadidi, and S.R. Moussa. 2009. Serum interleukin-18 expression in children with bronchial asthma. The World Allergy Organization Journal 2: 63–68.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kroeger, K.M., B.M. Sullivan, and R.M. Locksley. 2009. IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38alpha-dependent pathway. Journal of Leukocyte Biology 86: 769–778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Oda H., Kawayama T., Imaoka H., Sakazaki Y., Kaku Y., Okamoto M., et al. 2014. Interleukin-18 expression, CD8(+) T cells, and eosinophils in lungs of nonsmokers with fatal asthma. Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 112:23–28 e21.

  26. Sawada, M., T. Kawayama, H. Imaoka, Y. Sakazaki, H. Oda, S. Takenaka, et al. 2013. IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13. PloS One 8: e54623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Murai, H., H. Qi, B. Choudhury, J. Wild, N. Dharajiya, S. Vaidya, et al. 2012. Alternaria-induced release of IL-18 from damaged airway epithelial cells: an NF-kappaB dependent mechanism of Th2 differentiation? PloS One 7: e30280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by the Natural Science Foundation of China (81270011; 81472125).

Author information

Authors and Affiliations

  1. Department of Pediatrics, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, China

    Ming-Hui Xu, Feng-Lai Yuan, Shu-Jing Wang, Hui-Ying Xu, Cheng-Wan Li & Xiao Tong

Authors
  1. Ming-Hui Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Feng-Lai Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shu-Jing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hui-Ying Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cheng-Wan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Cheng-Wan Li or Xiao Tong.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, MH., Yuan, FL., Wang, SJ. et al. Association of interleukin-18 and asthma. Inflammation 40, 324–327 (2017). https://doi.org/10.1007/s10753-016-0467-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-016-0467-3

KEY WORDS

Search

Navigation