Independent and Combined Associations of Blood Manganese, Cadmium and Lead Exposures with the Systemic Immune-Inflammation Index in Adults

Abstract

Manganese (Mn), cadmium (Cd) and lead (Pb) have toxic effects on the immune system. However, their independent and combined effects on immune-inflammation responses are unclear. In recent years, the systemic immune-inflammation index (SII) has been developed as an integrated and novel inflammatory indicator. A retrospective cross-sectional study of 2174 adults ≥20 years old from the National Health and Nutrition Examination Survey (NHANES) 2015–2016 was conducted. Generalized linear models were used to evaluate the independent and combined associations of SII with blood Mn, Cd and Pb levels. As continuous variables, both blood Cd and Mn showed dose-dependent relationships with the SII before and after adjusting for all potential confounding factors. Metal concentrations were then converted into categorical variables. Compared with the adults in the lowest Cd or Mn tertile, those in the highest tertile had higher risks of elevated SII. Furthermore, co-exposure to Mn and Cd also showed a positive relationship with the SII after adjusting for all confounding factors. However, the single effect of Pb exposure and the joint effect of Pb and other metal exposures on the SII were not observed. This study provides important epidemiological evidence of the associations of SII with single and co-exposure effects of blood Mn, Cd, and Pb.

Association of Metal Exposure with Novel Immunoinflammatory Indicators

“…Consistent with previous results, our study did not find an association between Pb exposure and immunoinflammatory indicators, whether it was blood lead or mixture exposure [59]. We speculate that gender differences may play a role in mediating the immunoinflammatory response to metal exposure, possibly due to women's heightened sensitivity to metal exposure [60].…”

Association between multiple-heavy-metal exposures and systemic immune inflammation in a middle-aged and elderly Chinese general population

“…This perturbation may affect the regulation of immune-inflammatory responses in humans [ 17 , 18 ]. In addition, in a Chinese study, Zhong and his colleagues discovered that study participants with higher blood levels of manganese and cadmium had higher levels of SII [ 19 ]. Based on the abovementioned studies, we hypothesized that heavy metal exposure may have a potential association with immune-inflammatory markers in serum.…”

Effect of blood lead levels on periodontitis in American adults: a cross-sectional analysis from the national health and nutrition examination survey

“…With too much lead deposition, enamel is destroyed, teeth begin to fall out, and lead accumulation has toxic effects on dental nerves, which may lead to adverse reactions such as atrophy of dental nerves. In addition, blood lead can lead to an increase in the immune response [ 54 ] and the enhancement of immune cell activity, thus causing inflammation. Despite the gradual decrease in individuals’ blood lead levels in recent decades, the detrimental impact of elevated blood lead levels on periodontal disease risk persists, indicating that there is no safe threshold for blood lead levels; lower levels are preferable.…”