MMP-9 and TIMPs profiles in sulfur mustard-exposed individuals with serious lung complications

Abstract

Sulfur mustard (SM), a chemical weapon used in the Iraq-Iran war, can pose severe health risks, especially to the lungs. Dysregulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in various inflammatory lung diseases. This study compares the levels of MMPs and TIMPs in the serum and sputum of veterans with serious lung complications to a control group. Serum and sputum samples were collected and analyzed using the ELISA sandwich method. Differences between SM-exposed and control groups were assessed statistically. The serum levels of TIMP-4 and MMP-9/TIMP-4 were significantly lower and higher in the SM-exposed group respectively compared to the control group. In SM-exposed individuals resembling Bronchiolitis Obliterans (BO), Chronic Bronchitis (CB), and Asthma, TIMP-4 levels were lower than controls, while TIMP-2 levels were higher in those with CB. Although the increased TIMP-2 levels in these patients align with COPD studies, differences were observed in other factors with COPD and asthma-related MMP-9 and TIMP-4 findings. Assessment of serum levels of these factors based on severity reveals lower MMP-9/TIMP-4 levels in the severe group compared to the mild-moderate group. Individuals exposed to SM exhibit distinct MMP and TIMP profiles, with significantly lower TIMP-4 levels and higher MMP-9/TIMP-4 ratios, compared to controls. These profiles vary across different lung conditions, indicating a unique disease mechanism in SM-exposed individuals. This distinctive profile supports the classification of this condition as 'Mustard Lung.' Further research is needed to elucidate these mechanisms for targeted therapeutic interventions.

Keywords: Inflammatory lung diseases; MMP-9; MMP/TIMP ratio; Mustard lung; Sulfur mustard; TIMPs.