Regulation of human eotaxin generation by Th1-/Th2-derived cytokines

Int Arch Allergy Immunol. 2000 May;122 Suppl 1:54-8. doi: 10.1159/000053634.


Background: Accumulating evidence indicates that eotaxin is the primary mediator of tissue eosinophilia. In the present study, we analyzed the mechanisms of eotaxin generation by Th1-/Th2-derived cytokines in vitro.

Methods: Human dermal fibroblasts, human umbilical vein endothelial cells and A549 human bronchial epithelial cell line cells were stimulated with TNF-alpha, IL-4, IFN-gamma or TNF-alpha in combination with IL-4 or IFN-gamma and the amount of eotaxin production was analyzed.

Results: Fibroblasts produced nanogram/milliliter quantities of eotaxin. Proinflammatory cytokine TNF-alpha and Th2-type cytokine IL-4 each induced eotaxin production, and combination of them caused a marked synergistic increase in that production. On the other hand, Th1-type cytokine IFN-gamma inhibited eotaxin generation at the protein/mRNA levels.

Conclusion: The Th2-derived cytokine upregulated while the Th1-derived cytokine inhibited eotaxin production by fibroblasts. In view of the Th1/Th2 paradigm, these results indicate that (1) eotaxin regulates eosinophil accumulation in the Th2-dominant state such as allergic disease, and (2) direct suppression of eotaxin production by IFN-gamma is one of the major mechanisms by which IFN-gamma suppresses eosinophilic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chemokine CCL11
  • Chemokines, CC*
  • Cytokines / biosynthesis*
  • Cytokines / pharmacology*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-4 / pharmacology
  • Th1 Cells / physiology*
  • Th2 Cells / physiology*
  • Tumor Necrosis Factor-alpha / pharmacology


  • CCL11 protein, human
  • Chemokine CCL11
  • Chemokines, CC
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma