Long term impact of sulfur mustard exposure on peripheral blood mononuclear subpopulations — Sardasht-Iran Cohort Study (SICS)

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Abstract

The most important long-term morbidity problem of sulfur mustard (SM) toxicity is pulmonary complications but the pathogenesis of these complications is not clearly understood. This study evaluates the peripheral blood mononuclear sub-sets and their correlation with pulmonary function in SM exposed civilian cases 20 years post-exposure as gathered in the context of the Sardasht-Iran Cohort Study (SICS). Samples were randomly selected from two groups, SM-exposed (n = 372) and control (n = 128), with the same ethnicity, culture, and demography. Three color flow cytometry was applied for peripheral blood mononuclear sub-population determination. Results indicated a significant decrease in CD45 +/CD3 +, CD45 +/CD3 +/CD4 +, and an increase in CD3 +/CD16+56 + percentages. It was also found that absolute count of NK cells was highly increased in peripheral blood of exposed cases. There was a significant increase in NK cell count of SM exposed group with pulmonary problems as compared to the same group without pulmonary problems (p-value < 0.04) based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The findings showed a significant negative correlation between absolute numbers of T lymphocyte and FVC % and positive correlation with FEV1/FVC%. The results also demonstrated that absolute numbers of monocytes had a negative correlation with FVC %. We propose that NK and T cells are probably involved in the pathogenesis or immune reactions to the delayed pulmonary complications induced by SM. This hypothesis should be tested in a more severe pulmonary complicated group.

Highlights

► A significant decreased in CD45+/CD3+ and CD45+/CD3+/CD4+ percentages was found in peripheral blood of exposed cases. ► A significant increase in CD3+/CD16+56+ percentages and number was found in peripheral blood of exposed cases. ► An association was found between NK cell counts with pulmonary problems in SM exposed group. ► A negative correlation between absolute numbers of T lymphocyte and FVC % and positive correlation with FEV1/FVC was shown. ► NK and T cells are probably involved in the pathogenesis or control of the delayed SM induced pulmonary complications.

Introduction

The most important long-term morbidity problem of Sulfur Mustard (SM) toxicity is pulmonary complications but the pathogenesis of these complications is not clearly understood. As has been reported, SM exposure can lead to the development of a series of chronic destructive pulmonary complications. Different diagnoses including asthma, chronic bronchitis, bronchiectasis, airway narrowing due to searing or granulation tissue, pulmonary fibrosis [1] obliterative bronchiolitis (OB) [2], [3], bronchiolectasis, and chronic obstructive pulmonary disease (COPD) [4] were reported but there are unknown cell and molecular mechanisms underlying SM induced lung complications. It is well known that SM exposure has considerable impact on hematopoiesis and peripheral blood sub-sets. Few reports on long term effects of SM on leukocytes sub-sets have been published previously. It was shown that CD4 and CD8 T cells were decreased in SM exposed veterans long after exposure [5], [6], [7]. However, Mahmoudi et al. showed an increase in CD3 + and monocytes in SM exposed cases [8].

A significant depression has been reported on NK cells in veterans who had severe SM-related complications 16 years after exposure [8]. Low NK cell percentage was also reported in another study in severe SM exposed patients, however an elevation was reported in their NK activity [9].

To investigate long term complications of SM exposure and the underlying mechanism(s) a historical cohort study has been established, named ‘Sardasht-Iran Cohort Study’ (SICS) [10].

In this paper the results of peripheral blood mononuclear subsets and their correlations with SM induced pulmonary findings are reported.

Section snippets

Participants

The details of methodology of SICS was extensively described in the original methodology paper [10]. In SICS, 372 male participants from Sardasht, who were exposed to SM in 1987, were compared to 128 unexposed sex/age matched controls from the unexposed town of Rabat. SICS was initiated in 2006. The clinical evaluations and sample preparations were undertaken in 2007.

Ethical considerations

The study was approved by the Ethical committee of Board of Research Ethics of Janbazan Medical and Engineering Research Center

Results

There were no significant differences between the two groups in terms of age, Body Mass Index (kg/m2), marital status and smoking. The mean ± SD of the age in the control and SM exposed group were 41.7 ± 9.8and 43.8 ± 10.8 respectively.

Discussion

The pathology and the immunological mechanisms underlying pulmonary complications caused by SM are not clearly understood, however different pathological diagnoses have been reported including COPD [4], bronchiolectasis, oblitrative bronchiolitis [3] and pulmonary fibrosis [1].

The roles of different leukocyte sub-sets in lung inflammatory diseases have been demonstrated. In SM injuries there are controversial reports regarding the proportion of leukocyte sub-sets.

Hematological results showed a

Acknowledgment

This study was performed by the Immunoregulation Research Center (IRRC) of Shahed University and the Janbazan Medical and Engineering Research Center (JMERC) and supported by the Martyr and Veterans Affairs Foundation of Iran and the Ministry of Health and Medical Education. We would very kindly like to thank all of the participants who took part in this study. We also thank Dr Riazi and Dr Drabi for their technical assistant in Flowcytometry experiments.

Deceleration: Authors reported no

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