Background: Sulfur mustard (SM) is a chemical warfare agent that causes severe, long-term health complications characterized by persistent systemic inflammation. This study aimed to investigate the association between serum C-reactive protein (CRP) and leukocyte mitochondrial DNA copy number (mtDNA-CN) in leukocytes relative to SM exposure level.

Methods : This case-control study included 196 participants: 142 SM-exposed veterans (categorized into asymptomatic, mild, and severe subgroups) and 54 non-exposed controls. Serum CRP levels were measured using an enzyme-linked immunosorbent assay. Leukocyte mtDNA-CN was determined by quantitative real-time PCR (qPCR).

Results: Serum CRP levels were significantly elevated in the SM-exposed group compared to controls (P < 0.05), particularly in the severe subgroup. However, no significant difference in mtDNA-CN was found between the exposed and control groups. A significant positive correlation between CRP and mtDNA-CN was identified in the overall SM-exposed group and in the asymptomatic and mild subgroups. This positive correlation was not observed in the control group or the severe subgroup.

Conclusions :The findings reveal a nuanced, exposure-level-dependent relationship between inflammation and mitochondrial DNA content. The positive correlation in less severely affected individuals might suggest a potential adaptive upregulation of mitochondrial biogenesis in response to inflammation, which may falter in severe cases. These insights contribute to our understanding of the potential long-term biological impacts of SM exposure and might lead to future biomarker development and therapeutic strategies.