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

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.