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Metal exposures and their interactions with the dietary inflammatory index on inflammatory biomarkers in Mexican adolescents

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Overview

This prospective cohort study (n=399, ELEMENT birth cohort, Mexico City) examined associations between blood lead, urinary arsenic, and urinary cadmium with serum inflammatory biomarkers (IL-4, IL-1beta, IL-6, IL-8, IL-10, TNFalpha) and whether these associations were modified by the dietary inflammatory index (DII). The key finding is that cadmium was associated with lower IL-6 (immunosuppressive direction), while lead’s pro-inflammatory effects were amplified in adolescents consuming an anti-inflammatory diet. This interaction finding underlines that diet can modulate metal immunotoxicity in opposite directions depending on the metal and cytokine endpoint.

Key numbers

  • Sample: n=399 adolescents, ELEMENT birth cohort, Mexico City.
  • Blood lead: all above LOD (0.284 microg/dL); median 2.3 microg/dL.
  • Urinary arsenic: all above LOD (0.3 microg/L).
  • Urinary cadmium: 42.1% below LOD (0.06 microg/L).
  • Cadmium — IL-6 association: -14.5% per SD increase (95% CI: -23.4 to -4.5; FDR P=0.04). This is in the immunosuppressive direction.
  • In adolescents in the most anti-inflammatory dietary tertile (C-DII T1): blood lead was associated with higher IL-4, IL-1beta, IL-6, and IL-8 (P-trend < 0.05 for diet-metal interactions).
  • Associations expressed as percentage difference in inflammatory biomarker per SD increase in metal exposure.
  • No metal-cytokine association survived FDR correction in the full sample except cadmium/IL-6.

Methods (brief)

Cross-sectional analysis within a prospective cohort. Blood lead by graphite furnace atomic absorption spectrometry. Urinary arsenic and cadmium by ICP-MS. Cytokines (IL-4, IL-1beta, IL-6, IL-8, IL-10, TNFalpha) by multiplex immunoassay. Dietary inflammatory index computed from dietary recall. Linear regression adjusted for age, sex, BMI, socioeconomic status. Multiple testing correction by Benjamini-Hochberg FDR. LOD noted for each analyte; cadmium values below LOD substituted as LOD/sqrt(2). Speciation of arsenic not reported; total urinary arsenic used.

Limitations

Urinary cadmium is affected by kidney filtration efficiency and creatinine dilution; 42% of values below LOD limits cadmium effect estimates. Cross-sectional cytokine measurement subject to acute illness and diurnal variation. Total urinary arsenic does not distinguish inorganic from organic species.

Implications

Certification: Shows that low-level environmental lead exposure (median 2.3 microg/dL) modulates inflammatory cytokines in adolescents, with effect direction dependent on diet quality. HMT&C thresholds for lead (Pb) in food should account for this diet-exposure interaction.

Courses: Demonstrates that dietary context modifies metal immunotoxicity. Useful in courses on cumulative exposure and food-system interactions.

App: No food concentration data. Contributes to immune-endpoint framing for Pb, cadmium (Cd), and arsenic (As).

Microbiome: Does not address microbiota directly. Diet-immune interaction pathway noted for WikiBiome federation context.

Update history

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