Can inflammation lower serum zinc by redistributing it into tissues and immune cells?

Systemic inflammation triggered by infection, injury, or sterile stressors initiates a rapid, coordinated acute-phase response. This process significantly alters systemic micronutrient distribution, most notably resulting in a sharp decline in circulating zinc.

Clinical and physiological evidence

• Systemic inflammation rapidly induces transient hypozincemia, which represents an active redistribution of zinc rather than a true dietary or bodily deficiency.
• During the acute-phase response, zinc is mobilized out of the vascular compartment and sequestered within tissues (primarily the liver) and immune cells.

Mechanistic pathways of zinc redistribution

• The cascade is initiated by pro-inflammatory cytokines, primarily interleukin-6 (IL-6) and interleukin-1 (IL-1), which surge during acute inflammatory states.
• These cytokines directly upregulate the expression and plasma-membrane localization of the zinc importer ZIP14 (SLC39A14) on hepatocytes.
• Simultaneously, cytokine signaling stimulates the transcription of hepatic metallothioneins, which are low-molecular-weight, cysteine-rich proteins.
• Upregulated ZIP14 facilitates a major influx of zinc from the bloodstream into hepatocytes, where the newly imported zinc is rapidly bound and sequestered by metallothioneins, preventing its efflux.
• This temporary cellular sequestration serves vital adaptive roles, including supporting the synthesis of acute-phase proteins, providing intracellular antioxidant protection, and withholding essential zinc from circulating pathogens (nutritional immunity).

Bottom line

• Inflammatory hypozincemia is a highly regulated, protective physiological response—not a dietary deficiency—driven by cytokine-mediated upregulation of ZIP14 and metallothioneins that actively redistribute and sequester zinc in the liver.