Advertisement

Current status of the acquired immune system of Iranian patients with long-term complications of sulfur mustard poisoning

  • Mahdi Balali-Mood
  • Bamdad Riahi-Zanjani
  • Mahmoud Mahmoudi
  • Mahmood SadeghiEmail author
Research Article
First Online:
  • 16 Downloads

Abstract

Background

Sulfur mustard (SM) is a powerful blistering chemical warfare agent that has genotoxic effects. Cells with excessive proliferation such as lymphocytes may inherit this cellular toxicity which can lead to their malfunctions in the long-term. This study was designed to evaluate the status of acquired immunity among SM poisoned veterans around three decades after exposure.

Methods

Thirty five male Iranian veterans having at least 25% disability due to SM poisoning with long-term complications in the respiratory system, skin or eyes were investigated. Non-functional/functional tests including hematological parameters, immunostaining analysis, lymphocyte proliferation assay, cytokine profile, and levels of total serum IgM, IgG and IgA were performed.

Results

The results showed that most of the parameters of adaptive immune system of the veterans were currently within the normal ranges. However, changes in the proliferation index (PI) of lymphocytes showed problems with the lymphocytes which cannot be proliferated appropriately. PI values for PBMCs (peripheral blood mononuclear cells) in presence of PHA (Phytohemagglutinin-A) and LPS (lipopolysaccharide) mitogens were 1.16 ± 0.14 and 1.13 ± 0.07, respectively which are less than expected.

Conclusions

Based on the results gathered in this study, most of the parameters of acquired immunity were normal. However, the observed failure of lymphocyte functions may disrupt physiological activity of whole immune system leading to long-term complications; including recurrent respiratory tract infections. Indeed, further cellular and molecular studies with regard to lymphocytes function are required to better understand the status of adaptive immunity in these patients.

Graphical abstract

ᅟ

Keywords

Sulfur mustard Acquired immunity Veterans Adaptive immune system Lymphocytes 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

The authors are thankful to the Vice Chancellor of Research of Mashhad University of Medical Sciences and Organization for the Prohibition of Chemical Weapons for their financial supports. The authors are also grateful to Mehran Sadeghi for his contribution to the preparation of graphical abstract. The results of the present study are part of a PhD thesis of Mahmood Sadeghi.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. 1.
    Keramati MR, Balali-Mood M, Mousavi SR, Sadeghi M, Riahi-Zanjani B. Biochemical and hematological findings of Khorasan veterans 23 years after sulfur mustard exposure. J Res Med Sci. 2013;18:855–9.Google Scholar
  2. 2.
    Namazi S, Niknahad H, Razmkhah H. Long-term complications of sulphur mustard poisoning in intoxicated Iranian veterans. J Med Toxicol. 2009;5:191–5.CrossRefGoogle Scholar
  3. 3.
    Ghabili K, Agutter PS, Ghanei M, Ansarin K, Shoja MM. Mustard gas toxicity: the acute and chronic pathological effects. J Appl Toxicol. 2010;30:627–43.CrossRefGoogle Scholar
  4. 4.
    Reid F, Graham J, Niemuth N, Singer A, Janny S, Johnson J. Sulfur mustard-induced skin burns in weanling swine evaluated clinically and histopathologically. J Appl Toxicol. 2000;20:153–60.CrossRefGoogle Scholar
  5. 5.
    Razavi SM, Salamati P, Saghafinia M, Abdollahi M. A review on delayed toxic effects of sulfur mustard in Iranian veterans. DARU J Pharmaceut Sci. 2012;20:51–8.CrossRefGoogle Scholar
  6. 6.
    Simpson R, Lindsay CD. Effect of sulphur mustard on human skin cell lines with differential agent sensitivity. J Appl Toxicol. 2005;25:115–28.CrossRefGoogle Scholar
  7. 7.
    Heinrich A, Balszuweit F, Thiermann H, Kehe K. Rapid simultaneous determination of apoptosis, necrosis, and viability in sulfur mustard exposed HaCaT cell cultures. Toxicol Lett. 2009;191:260–7.CrossRefGoogle Scholar
  8. 8.
    Riahi-Zanjani B, Balali-Mood M. Aflatoxin M 1 contamination in commercial pasteurized milk from local markets in Fariman, Iran. Mycotoxin Res. 2013;29:271–4.CrossRefGoogle Scholar
  9. 9.
    Korkmaz A, Tan DX, Reiter RJ. Acute and delayed sulfur mustard toxicity; novel mechanisms and future studies. Interdiscip Toxicol. 2008;1:22–6.Google Scholar
  10. 10.
    Rowell M, Kehe K, Balszuweit F, Thiermann H. The chronic effects of sulfur mustard exposure. Toxicology. 2009;263:9–11.CrossRefGoogle Scholar
  11. 11.
    Hassan ZM, Ebtekar M, Ghanei M, Taghikhani M, Noori Daloii MR, Ghazanfari T. Immunobiological consequences of sulfur mustard contamination. Iran J Allergy Asthma Immunol. 2006;5:101–8.Google Scholar
  12. 12.
    Balali-Mood M, Hefazi M. The pharmacology, toxicology, and medical treatment of Sulphur mustard poisoning. Fundam Clin Pharmacol. 2005;19:297–315.CrossRefGoogle Scholar
  13. 13.
    Balali-Mood M, Hefazi M. Comparison of early and late toxic effects of sulfur mustard in Iranian veterans. Basic Clin Pharmacol Toxicol. 2006;99:273–82.CrossRefGoogle Scholar
  14. 14.
    Balali-Mood M, Hefazi M, Mahmoudi M, Jalali E, Attaran D, Maleki M, et al. Long-term complications of sulphur mustard poisoning in severely intoxicated Iranian veterans. Fundam Clin Pharmacol. 2005;19:713–21.CrossRefGoogle Scholar
  15. 15.
    Balali-Mood M, Mousavi S, Balali-Mood B. Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans. Emerg Health Threats J. 2008;1:7068.CrossRefGoogle Scholar
  16. 16.
    Balali-Mood M, Afshari R, Zojaji R, Kahrom H, Kamrani M, Attaran D, et al. Delayed toxic effects of sulfur mustard on respiratory tract of Iranian veterans. Hum Exp Toxicol. 2011;30:1141–9.CrossRefGoogle Scholar
  17. 17.
    Hefazi M, Maleki M, Mahmoudi M, Tabatabaee A, Balali-Mood M. Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16-20 years after exposure. Int J Dermatol. 2006;45:1025–31.CrossRefGoogle Scholar
  18. 18.
    Riahi-Zanjani B, Mahmoudi M. Immunological and hematological complications of sulfur mustard poisoning. In: Balali-Mood M, Abdollahi M, editors. Basic and clinical toxicology of mustard compounds. Switzerland: Springer; 2015.Google Scholar
  19. 19.
    Mahmoudi M, Hefazi M, Rastin M, Balali-Mood M. Long-term hematological and immunological complications of sulfur mustard poisoning in Iranian veterans. Int Immunopharmacol. 2005;5:1479–85.CrossRefGoogle Scholar
  20. 20.
    Ghazanfari T, Kariminia A, Yaraee R, Faghihzadeh S, Ardestani SK, Ebtekar M, et al. Long term impact of sulfur mustard exposure on peripheral blood mononuclear subpopulations--Sardasht-Iran cohort study (SICS). Int Immunopharmacol. 2013;17:931–5.CrossRefGoogle Scholar
  21. 21.
    Mohammadhoseiniakbari H, Ghanei M, Eajazi A, Mohammadi Z, Daftari BL. Delayed effects of sulfur mustard poisoning on CD4+ and CD8+ lymphocytes in Iranian veterans 25 years after exposure. Med Sci Monit. 2008;14:CR580–3.Google Scholar
  22. 22.
    Ghasemi H, Ghazanfari T, Yaraee R, Pourfarzam S, Soroush MR, Faghihzadeh S, et al. Evaluation of the tear and serum levels of IL-8 in sulfur mustard intoxicated patients 20 years after exposure. Cutan Ocul Toxicol. 2012;31:132–7.CrossRefGoogle Scholar
  23. 23.
    Attaran D, Lari SM, Towhidi M, Marallu HG, Ayatollahi H, Khajehdaluee M, et al. Interleukin-6 and airflow limitation in chemical warfare patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2010;5:335–40.Google Scholar
  24. 24.
    Pourfarzam S, Ghazanfari T, Yaraee R, Ghasemi H, Hassan ZM, Faghihzadeh S, et al. Serum levels of IL-8 and IL-6 in the long term pulmonary complications induced by sulfur mustard: Sardasht-Iran cohort study. Int Immunopharmacol. 2009;9:1482–8.CrossRefGoogle Scholar
  25. 25.
    Attar M, Molaie Kondolousy Y, Khansari N. Effect of high dose natural ionizing radiation on the immune system of the exposed residents of Ramsar town. Iran Iran J Allergy Asthma Immunol. 2007;6:73–8.Google Scholar
  26. 26.
    Molaae N, Mosayebi G, Pishdadian A, Ejtehadifar M, Ganji A. Evaluating the proliferation of human PeripheralBlood mononuclear cells using MTT assay. Int J Basic Sci Med. 2017;2:25–8.CrossRefGoogle Scholar
  27. 27.
    Shaker Z, Hassan ZM, Sohrabpoor H, Mosaffa N. The immunostatus of T helper and T cytotoxic cells in the patients ten years after exposure to sulfur mustard. Immunopharmacol Immunotoxicol. 2003;25:423–30.CrossRefGoogle Scholar
  28. 28.
    Riahi-Zanjani B, Balali-Mood M, Mousavi SR, Karimi G, Sadeghi M, Shirmast E, et al. Serum cytokine profiles of Khorasan veterans 23 years after sulfur mustard exposure. Cytokine. 2014;70:161–4.CrossRefGoogle Scholar
  29. 29.
    Khateri S, Balali-Mood M, Blain P, Williams F, Jowsey P, Soroush MR, et al. DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure. Toxicol Lett. 2018;293:67–72.CrossRefGoogle Scholar
  30. 30.
    Riahi-Zanjani B, Balali-Mood M, Mahmoudi M, Sadeghi M. Innate immune system status of Sulphur mustard-poisoned Iranian veterans three decades after exposure. Basic Clin Pharmacol Toxicol. 2018;123:635–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mahdi Balali-Mood
    • 1
  • Bamdad Riahi-Zanjani
    • 2
  • Mahmoud Mahmoudi
    • 3
  • Mahmood Sadeghi
    • 2
    Email author
  1. 1.Medical Toxicology and Drug Abuse Research CenterBirjand University of Medical SciencesBirjandIran
  2. 2.Medical Toxicology Research CenterMashhad University of Medical SciencesMashhadIran
  3. 3.Immunology Research CenterMashhad University of Medical SciencesMashhadIran

Personalised recommendations

Cite article

Buy options