Zinc and regulation of inflammatory cytokines: implications for cardiometabolic disease

Nutrients. 2012 Jul;4(7):676-94. doi: 10.3390/nu4070676. Epub 2012 Jul 4.


In atherosclerosis and diabetes mellitus, the concomitant presence of low-grade systemic inflammation and mild zinc deficiency highlights a role for zinc nutrition in the management of chronic disease. This review aims to evaluate the literature that reports on the interactions of zinc and cytokines. In humans, inflammatory cytokines have been shown both to up- and down-regulate the expression of specific cellular zinc transporters in response to an increased demand for zinc in inflammatory conditions. The acute phase response includes a rapid decline in the plasma zinc concentration as a result of the redistribution of zinc into cellular compartments. Zinc deficiency influences the generation of cytokines, including IL-1β, IL-2, IL-6, and TNF-α, and in response to zinc supplementation plasma cytokines exhibit a dose-dependent response. The mechanism of action may reflect the ability of zinc to either induce or inhibit the activation of NF-κB. Confounders in understanding the zinc-cytokine relationship on the basis of in vitro experimentation include methodological issues such as the cell type and the means of activating cells in culture. Impaired zinc homeostasis and chronic inflammation feature prominently in a number of cardiometabolic diseases. Given the high prevalence of zinc deficiency and chronic disease globally, the interplay of zinc and inflammation warrants further examination.

Keywords: atherosclerosis; cytokines; diabetes mellitus; inflammation; zinc.

Publication types

  • Review

MeSH terms

  • Animals
  • Atherosclerosis / physiopathology*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Chronic Disease
  • Cytokines / genetics*
  • Cytokines / metabolism
  • Diabetes Mellitus / physiopathology*
  • Dietary Supplements
  • Gene Expression Regulation
  • Humans
  • Inflammation / physiopathology*
  • Interleukin-1beta / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-6 / metabolism
  • Models, Animal
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Zinc / administration & dosage
  • Zinc / deficiency
  • Zinc / metabolism*


  • Cation Transport Proteins
  • Cytokines
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Zinc