Changes in Inflammatory Cytokines, Antioxidants and Liver Stiffness after Chelation Therapy in Individuals with Chronic Lead Poisoning

Background Chronic exposure to lead accumulates mainly in the liver. In vivo studies showed that lead toxicities are related to alterations of the inflammatory response. We aimed to evaluate the association between lead poisoning and liver fibrosis as well as the change in degree of liver fibrosis, levels of inflammatory mediators and glutathione (GSH) after chelation therapy.

Methods Workers from a battery factory who were exposed to lead for > 12 months and had blood lead level (BLL) > 70 µg/dL were enrolled (n=86) into the study. They received chelation therapy with intravenous CaNa2EDTA for 2 days followed by oral D-penicillamine for 90 days. Primary outcome was the change in the degree of liver fibrosis, which was presented as liver stiffness (LS), measured by FibroScan®. Secondary outcomes were the change in the levels of serum GSH and inflammatory mediators such as tumor necrotic factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) after chelation therapy.

Results Of the 86 participants, there was a positive correlation between duration of lead exposure and LS (r=0.249, p=0.021). To avoid the confounder effect of obesity-related steatosis, only 70 individuals who had controlled attenuation parameters < 296 dB/m, BMI ≤ 25 kg/m2 and normal waist circumference were included in the interventional analysis. After chelation, the mean LS significantly decreased from 5.4 ± 0.9 to 4.8 ± 1.4 kPa (p=0.001). Similarly, all of the inflammatory cytokines studied significantly decreased after chelation (p<0.001); TNF-α dropped from 371.6 ± 211.3 to 215.8 ± 142.7; the levels of IL-1β dropped from 29.8 ± 1.7 to 25.9 ± 4.3 and the levels of IL-6 dropped from 46.8 ± 10.2 to 35.0 ± 11.9. On the other hand, the mean GSH level significantly increased from 3.3 ± 3.3 to 13.1 ± 3.7 (p<0.001) after chelation therapy.

Conclusions Our findings suggest that long-term exposure of lead may cause liver fibrosis. Lead poisoning induces chronic inflammatory response and oxidative stress. Treatment by chelation decreases inflammation and replenishes antioxidants, and potentially reduces the degree of LS.