Serum and sputum levels of IL-17, IL-21, TNFα and mRNA expression of IL-17 in sulfur mustard lung tissue with long term pulmonary complications (28 years after sulfur mustard exposure).

BACKGROUND: Iranian veterans who had exposed to Sulfur Mustard (SM) suffer from long term complications such as Chronic Obstructive Pulmonary Disease (COPD) and bronchiolitis obliterate (BO). Th17 cells product IL-17A, IL-17F, IL-21, and IL-22. They have important roles in chronic inflammatory diseases. Also, TNFα has a major part in pathobiological processes of COPD. In this study, we evaluate the serum and sputum levels of IL-17, IL-21, TNF-α, and mRNA expression of IL-17 in the lung tissue of the patients 28 years after SM exposure. MATERIAL AND METHOD: The cytokine levels of IL-17, IL-21 and TNFα were measured by ELISA method in serum and sputum of 455 SM-exposed and 123 unexposed people participated in Sardasht-Iran Cohort Study (SICS) of chemical victims. The mRNA expression of IL-17 was evaluated with qRT-PCR in lung biopsies (SM-exposed =52, control =33). Analyses of all data were accomplished with the SPSS software with P value ≤05. RESULT: The results show the sputum level of IL-17 in the exposed group decreased significantly compared to control group (P = 0.007) and Veterans and Martyrs Affair Foundation (VMAF) assessment was significantly lower in abnormal/exposed than normal/exposed group (P = 0.042). There were no significant differences between control and exposed groups in serum level of IL-17; also serum and sputum levels of IL-21, TNF-α, and IL-17 mRNA expression. CONCLUSION: Conclusively, The IL-17 level decreased in the exposed group. This decline could cause by mutation on transcription factors like Signal transducer and activator of transcription 3 gene (STAT3) or CCL20 as a chemokine.

Peripheral blood mononuclear cellular viability and its correlation with long-term pulmonary complications after sulfur mustard exposure.

INTRODUCTION: Sulfur mustard (SM) as a chemical warfare agent has short- and long-term complications on its victims. Complications of exposure to SM depend on the level of contamination. Long-term pulmonary complications are the most serious problems. Recent evidence has shown that absorbed SM can be conducted to other tissues by the bloodstream. In this study, we evaluated the long-term effects of SM on the vital activity of peripheral blood mononuclear cells (PBMCs) in SM-exposed patients with long-term pulmonary complications. MATERIALS AND METHODS: Our study samples were 110 patients with long-term pulmonary complications in the SM-exposed group and 109 unexposed individuals in the control group. After clinical examination and pulmonary function tests, the severity of pulmonary complications was classified. Also, the participants' peripheral blood was taken into EDTA-treated Vacutainer tubes. Then, the complete blood count (CBC) was calculated, and PBMCs was purified from whole blood using Ficol-Paque gradient method, finally, the vital activity was assessed by MTT assay. RESULT: The vital activity of PBMCs in the SM-exposed group with the mitogen was significantly lower than that in the control group (P = 0.016). Whereas, there was no significant difference in the viability of PBMCs without the mitogen between two groups. Furthermore, hematologic findings indicated that the SM-exposed group had a significant increase in the total count of WBC, neutrophil, MCV, and HCT values but the lymphocyte count and MCHC value were significantly lower than those in the control group. CONCLUSION: Exposure to SM even after a long time, can affect hematologic parameters and vital activity of PBMCs.

Circulating mesenchymal stem cells in sulfur mustard-exposed patients with long-term pulmonary complications.

Sulfur mustard (SM) is a toxic agent that causes acute and long-term pulmonary complications. Recent evidence has shown the impact of SM on mesenchymal stem cells (MSCs). These cells have a critical role in repairing the damaged tissues. In this study, we evaluated the mobilization of MSCs in SM-exposed patients with long-term pulmonary complications. Fifty-nine SM-injured patients with prolonged pulmonary complications and 20 healthy individuals were included. Patients were classified based on taking drugs, having comorbidities, and severity of respiratory consequence. MSCs with phenotype of CD45-CD44+CD29+CD105+ were evaluated in peripheral blood using flow cytometry. Circulating MSCs were lower in SM-exposed patients compared to the control group (0.93 vs. 2.72 respectively, P = 0.005). No significant difference was observed in the MSC count between patients taking corticosteroids or antibiotics and those patients not taking them. Comorbidities like liver and kidney diseases had changed the count of MSCs in SM-exposed subjects. In addition, the frequency of MSCs did not show any association with the severity of long-term pulmonary complications. In conclusion, SM-exposure causes a decline in the frequency of circulating MSCs in survivors. The lower number of the peripheral MSC population in SM-exposed patients was not affected by taking corticosteroids or antibiotics, but comorbidities are probably involved in MSC frequency. The decreases observed in the number of circulating MSCs was not associated with the severity of the pulmonary complications; however, further studies in mustard lung models are required to demonstrate the therapeutic or pathologic role of MSCs in SM injuries.