Suitability of macrophage inflammatory protein-1beta production by THP-1 cells in differentiating skin sensitizers from irritant chemicals

Contact Dermatitis. 2008 Apr;58(4):193-8. doi: 10.1111/j.1600-0536.2007.01311.x.

Abstract

Background: Worldwide restrictions in animal use for research have driven efforts to develop alternative methods.

Objective: The study aimed to test the efficacy of the macrophage inflammatory protein-1beta (MIP-1beta) assay for testing chemicals' skin-sensitizing capacity.

Methods: The assay was performed using 9 chemicals judged to be sensitizing and 7 non-sensitizing by the standard in vivo assays. THP-1 cells were cultured in the presence or absence of 4 doses, 0.01x, 0.1x, 0.5x, or 1x IC(50) (50% inhibitory concentration for THP-1 cell proliferation) of these chemicals for 24 hr, and the MIP-1beta level in the supernatants was determined. Skin sensitization by the test chemicals was determined by MIP-1beta production rates. The MIP-1beta production rate was expressed as the relative increase in MIP-1beta production in response to chemical treatment compared with vehicle treatment.

Results and conclusion: When the threshold MIP-1beta production rate used was 100% or 105% of dimethyl sulfoxide, all the sensitizing chemicals tested (dinitrochlorobenzene, hexyl cinnamic aldehyde, eugenol, hydroquinone, dinitrofluorobenzene, benzocaine, nickel, chromium, and 5-chloro-2-methyl-4-isothiazolin-3-one) were positive, and all the non-sensitizing chemicals (methyl salicylate, benzalkonium chloride, lactic acid, isopropanol, and salicylic acid), with the exception of sodium lauryl sulfate, were negative for MIP-1beta production. These results indicate that MIP-1beta could be a biomarker for classification of chemicals as sensitizers or non-sensitizers.

Publication types

  • Evaluation Study

MeSH terms

  • Allergens / pharmacology*
  • Allergens / toxicity
  • Animal Testing Alternatives / methods*
  • Animals
  • Biological Assay / methods*
  • Biomarkers / metabolism
  • Cell Line
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemokine CCL4 / biosynthesis*
  • Enzyme-Linked Immunosorbent Assay
  • Guinea Pigs
  • Humans
  • Inhibitory Concentration 50
  • Irritants / pharmacology*
  • Irritants / toxicity
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Skin / drug effects
  • Statistics, Nonparametric
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Allergens
  • Biomarkers
  • Chemokine CCL4
  • Irritants
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue