Induction of cytokine (interleukin-1alpha and tumor necrosis factor-alpha) and chemokine (CCL20, CCL27, and CXCL8) alarm signals after allergen and irritant exposure

Exp Dermatol. 2005 Feb;14(2):109-16. doi: 10.1111/j.0906-6705.2005.00226.x.


The immune system is called into action by alarm signals generated from injured tissues. We examined the nature of these alarm signals after exposure of skin residential cells to contact allergens (nickel sulfate and potassium dichromate) and a contact irritant [sodium dodecyl sulfate (SDS)]. Nickel sulfate, potassium dichromate, and SDS were applied topically to the stratum corneum of human skin equivalents. A similar concentration-dependent increase in chemokine (CCL20, CCL27, and CXCL8) secretion was observed for all three chemicals. Exposure to nickel sulfate and SDS was investigated in more detail: similar to chemokine secretion, no difference was observed in the time- and concentration-dependent increase in pro-inflammatory cytokine [interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha)] secretion. Maximal increase in IL-1alpha secretion occurred within 2 h after exposure to both nickel sulfate and SDS and prior to increased chemokine secretion. TNF-alpha secretion was detectable 8 h after chemical exposure. After allergen or irritant exposure, increased CCL20 and CXCL8, but not CCL27, secretion was inhibited by neutralizing human antibodies to either IL-1alpha or TNF-alpha. Our data show that alarm signals consist of primary and secondary signals. IL-1alpha and TNF-alpha are released as primary alarm signals, which trigger the release of secondary chemokine (CCL20 and CXCL8) alarm signals. However, some chemokines, for example, CCL27 can be secreted in an IL-1alpha and TNF-alpha independent manner. Our data suggest that skin residential cells respond to both allergen and irritant exposure by releasing mediators that initiate infiltration of immune responsive cells into the skin.

MeSH terms

  • Allergens / metabolism
  • Caustics / pharmacology
  • Cells, Cultured
  • Chemokine CCL20
  • Chemokine CCL27
  • Chemokines, CC / biosynthesis*
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1 / biosynthesis*
  • Interleukin-1 / metabolism
  • Interleukin-8 / biosynthesis*
  • Irritants / pharmacology
  • Keratinocytes / cytology
  • Macrophage Inflammatory Proteins / biosynthesis*
  • Nickel / pharmacology
  • Potassium Dichromate / pharmacology
  • Recombinant Proteins / chemistry
  • Skin / drug effects*
  • Skin / metabolism
  • Sodium Dodecyl Sulfate / pharmacology
  • Surface-Active Agents / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Allergens
  • CCL20 protein, human
  • CCL27 protein, human
  • Caustics
  • Chemokine CCL20
  • Chemokine CCL27
  • Chemokines, CC
  • Cytokines
  • Interleukin-1
  • Interleukin-8
  • Irritants
  • Macrophage Inflammatory Proteins
  • Recombinant Proteins
  • Surface-Active Agents
  • Tumor Necrosis Factor-alpha
  • Sodium Dodecyl Sulfate
  • nickel sulfate
  • Nickel
  • Potassium Dichromate