title: Topical cis-urocanic acid attenuates oedema and erythema in acute and subacute skin inflammation in the mouse.
abstract: BACKGROUND
  cis-Urocanic acid (cis-UCA) is an endogenous immunosuppressive molecule of the epidermis.
  
  
  OBJECTIVE
  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.
authors.affiliation: BioCis Pharma Ltd, Itainen Pitkakatu 4 B, FI-20520 Turku, Finland. jarmo.laihia@biocis.com
authors.forename: J K
authors.initials: JK
authors.lastname: Laihia
authors.forename: P
authors.initials: P
authors.lastname: Taimen
authors.forename: H
authors.initials: H
authors.lastname: Kujari
authors.forename: L
authors.initials: L
authors.lastname: Leino
mesh_terms: D000208:Acute Disease; D000279:Administration, Cutaneous; D000818:Animals; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000633:toxicity; D003875:Drug Eruptions / Q000188:drug therapy* / Q000209:etiology; D004487:Edema / Q000188:drug therapy*; D004890:Erythema / Q000188:drug therapy*; D007509:Irritants / Q000633:toxicity; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D014560:Urocanic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D003879:Dermatologic Agents; D007509:Irritants; D014560:Urocanic Acid; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide