Abstract
BackgroundIn clinical studies, the findings on sulfur mustard (SM) toxicity for CD3+CD4+ and CD3+CD8+ T lymphocyte subsets are contradictory. In animal experiments, the effect of SM on the T cell number and proliferation is incompatible and is even the opposite of the results in human studies. In this study, we observed the dynamic changes of T lymphocytes in the first week in a high-dose SM-induced model.MethodsMice were exposed to SM by subcutaneous injection (20 mg/kg) and were sacrificed 4 h, 24 h, 72 h and 168 h later. Spleen T lymphocyte proliferation was evaluated by 3H-TdR. Flow cytometric analysis was used to observe the percentage of CD3+CD4+ and CD3+CD8+ T lymphocyte subsets. The IL-1β, IL-6, IL-10 and TNF-α levels in plasma were assayed using the Luminex method. DNA damage in bone marrow cells was observed with the single cell gel electrophoresis technique (SCGE).ResultsSM continuously inhibited the proliferation of lymphocytes for 7 days, and there was a significant rebound of Con A-induced T lymphocyte proliferation only at 24 h. The percentage of CD3+CD4+ and CD3+CD8+ lymphocytes was upregulated, which was accompanied by increased IL-1β and TNF-α and decreased IL-10. The IL-6 level was gradually decreased in the PG group at 4 h. The peak of lymphocytic apoptosis and DNA damage occurred at 24 h and 72 h, respectively.ConclusionOur results show that SM significantly inhibited T lymphocyte proliferation as well as induced CD3+CD4+ and CD3+CD8+ upregulation. SM intoxication also significantly increased the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and inhibited the level of anti-inflammatory cytokine IL-10. Our results may partly be due to the significant SM induced significant apoptosis and necrosis of lymphocytes as well as DNA damage of bone marrow cells. The results provided a favorable evaluation of SM immune toxicity in an animal model.
Highlights
In clinical studies, the findings on sulfur mustard (SM) toxicity for CD3+CD4+ and CD3+CD8+ T lymphocyte subsets are contradictory
There was no significant difference in the spleen weight or coefficient between the SM group and solvent treatment group (PG group) at 4 h
Several researchers found that peripheral blood T lymphocytes, monocytes, macrophages, neutrophils, endothelial and epithelial cells in the gut as well as bone marrow cells were sensitive to SM
Summary
The findings on sulfur mustard (SM) toxicity for CD3+CD4+ and CD3+CD8+ T lymphocyte subsets are contradictory. We observed the dynamic changes of T lymphocytes in the first week in a high-dose SM-induced model. Research in humans showed that, 20 years after the SM exposure, the severely affected victims of the Iran-Iraq war had a lower CD3+CD4+ level and higher CD3+CD8+ level in plasma compared to normal controls [13]. Different types of animals, SM doses, exposure routes, and observation times were used. These differences would cause inconsistent conclusions about the effect of SM on T lymphocyte proliferation and CD3+CD4+ and CD3+CD8+ T subsets. We constructed a high dose SM (20 mg/kg) exposure mouse model and observed the dynamic state of T lymphocyte function in this research. The homeostasis of proinflammatory and anti-inflammatory cytokines in lymphocytes, apoptosis, necrosis, and DNA damage of bone marrow cells were studied, which would help elucidate the process of SM-induced immune system damage [16,17,18]
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