The effects of iron deficiency on lymphocyte cytokine production and activation: preservation of hepatic iron but not at all cost

Clin Exp Immunol. 2001 Dec;126(3):466-73. doi: 10.1046/j.1365-2249.2001.01707.x.


Worldwide, over 40% of children have iron deficiency anaemia, frequently associated with infections. Certain cytokines are involved in both immune activation/response to infection and iron transport/metabolism. We therefore assessed the relations among iron deficiency, cytokine production and lymphocyte activation markers in 142 hospitalized Malawian children. We examined peripheral blood lymphocyte antigens/cytokine production using four- colour flow cytometry and serum transferrin receptor (TfR) levels, an inverse measure of iron status unaffected by acute illness or infection, with an enzyme-linked immunosorbent assay. Wilcoxon rank sum tests and logistic regression analyses (LRA) were performed. Iron deficiency (TfR > or = 10 microg/ml) versus TfR < 10 microg/ml, was associated with higher percentages of lymphocytes producing: (a) induced or spontaneous IL-6 (medians: induced, 15.9% for iron-deficient children versus 8.8% for iron-replete children, P = 0.002; spontaneous, 24.4% versus 13.0%, P < 0.001) and (b) induced IFN-gamma (medians:18.4% versus 12.4%, P = 0.006). The percentages of CD8(+) T cells spontaneously producing IL-6 and of all lymphocytes producing induced TNF-alpha and IFN-gamma in the same cell had the strongest relationships to iron deficiency (b = + 0.0211, P = 0.005 and b = + 0.1158, P = 0.012, respectively, LRA) and were also positively related to the co-expression of the T cell activation markers HLA DR and CD38. Severe iron deficiency (TfR > or = 30 microg/ml) was associated with the percentage of lymphocytes producing induced IL-4 (medians: 0.5% versus 1.6%, P < 0.010). The cytokine patterns associated with iron deficiency in our study would preserve iron stores but also preferentially retain the activation capabilities of T cells, albeit not necessarily other immune cells, until a critical level of iron depletion is reached.

MeSH terms

  • Adolescent
  • Anemia, Iron-Deficiency / immunology
  • Anemia, Iron-Deficiency / metabolism
  • Child
  • Child, Preschool
  • Cytokines / biosynthesis*
  • Female
  • Humans
  • Immunity, Cellular
  • In Vitro Techniques
  • Infant, Newborn
  • Interferon-gamma / biosynthesis
  • Interleukin-6 / biosynthesis
  • Iron Deficiencies*
  • Liver / metabolism*
  • Lymphocyte Activation
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism*
  • Male
  • Receptors, Transferrin / blood
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Cytokines
  • Interleukin-6
  • Receptors, Transferrin
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma