Topical application of FK506 (tacrolimus) ointment inhibits mite antigen-induced dermatitis by local action in NC/Nga mice

Int Arch Allergy Immunol. 2004 Jan;133(1):55-63. doi: 10.1159/000076128. Epub 2004 Jan 12.

Abstract

Background: FK506 ointment (tacrolimus ointment, protopic) is a new drug therapeutically effective for patients with atopic dermatitis (AD). However, the mechanism of action of FK506 ointment on AD is not fully understood.

Methods: We examined the effect of FK506 ointment on mite antigen-induced dermatitis in NC/Nga mice. Clinical symptoms and ear thickness were recorded, and histopathological studies and in vitro analyses were performed.

Results: Topical application of FK506 ointment (0.03-0.3%) suppressed the development of dermatitis. In the lesional skin, both interleukin (IL)-4 and interferon (IFN)-gamma were detected, even though the IL-4+/IFN-gamma- T helper 2 (Th2) population was predominant in the regional lymph nodes (LNs). Topical application of FK506 treatment reduced the elevated level of both IL-4 and IFN-gamma in the skin, but did not decrease the expansion of the Th2 population in the LNs.

Conclusions: Topical application of FK506 ointment suppresses dermatitis by inhibiting the activation of inflammatory cells locally, without systemic immune suppression, in this AD model.

MeSH terms

  • Administration, Topical
  • Animals
  • Antigens, Dermatophagoides / immunology
  • CD4 Antigens / metabolism
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / pathology
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Immunohistochemistry
  • Immunosuppressive Agents / administration & dosage*
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-4 / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred Strains
  • Specific Pathogen-Free Organisms
  • Tacrolimus / administration & dosage*
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antigens, Dermatophagoides
  • CD4 Antigens
  • Immunosuppressive Agents
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interleukin-4
  • Interferon-gamma
  • Tacrolimus