Topical cis-urocanic acid attenuates oedema and erythema in acute and subacute skin inflammation in the mouse

Br J Dermatol. 2012 Sep;167(3):506-13. doi: 10.1111/j.1365-2133.2012.11026.x. Epub 2012 Jul 19.

Abstract

Background: cis-Urocanic acid (cis-UCA) is an endogenous immunosuppressive molecule of the epidermis.

Objectives: We investigated the effects of topical cis-UCA creams (2·5% and 5%) in acute and subacute mouse models of skin inflammation.

Methods: Acute skin irritation was induced by applying dimethyl sulphoxide (DMSO) on the earlobe of CD-1 mice. Topical cis-UCA, hydrocortisone (1%) or tacrolimus (0·1%) were applied 10 min later. In another model, subacute inflammation was provoked and maintained by three applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the ears of NMRI mice on days 1, 2 and 4. The test products were applied topically twice a day during 6 days.

Results: In the acute DMSO model, cis-UCA creams suppressed ear swelling at 1 h significantly more efficiently than hydrocortisone (P < 0·01) and tacrolimus (P < 0·001). Ear swelling was significantly inhibited by cis-UCA (P < 0·001) in the subacute TPA model as well. The 5% cream also decreased erythema, whereas tacrolimus enhanced skin reddening. Treatments with cis-UCA did not affect TPA-induced infiltration of neutrophils to the skin. In contrast to hydrocortisone, cis-UCA did not reduce epidermal thickness.

Conclusions: The results suggest that cis-UCA - unlike hydrocortisone and tacrolimus - is efficient in both acute and subacute skin inflammation, attenuating skin oedema and erythema. Topical drug therapy with cis-UCA may provide a safe and effective drug treatment modality in inflammatory skin disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Administration, Cutaneous
  • Animals
  • Dermatologic Agents / administration & dosage
  • Dermatologic Agents / pharmacology*
  • Dimethyl Sulfoxide / toxicity
  • Drug Eruptions / drug therapy*
  • Drug Eruptions / etiology
  • Edema / drug therapy*
  • Erythema / drug therapy*
  • Irritants / toxicity
  • Male
  • Mice
  • Neutrophil Infiltration / drug effects
  • Tetradecanoylphorbol Acetate / analogs & derivatives
  • Tetradecanoylphorbol Acetate / toxicity
  • Urocanic Acid / administration & dosage
  • Urocanic Acid / pharmacology*

Substances

  • 12-O-tetradecanoylphorbol-1,3-acetate
  • Dermatologic Agents
  • Irritants
  • Urocanic Acid
  • Tetradecanoylphorbol Acetate
  • Dimethyl Sulfoxide