The effect of topical FK506 (tacrolimus) in a mouse model of allergic rhinitis

Am J Rhinol Allergy. 2012 Mar-Apr;26(2):e71-5. doi: 10.2500/ajra.2012.26.3743.

Abstract

Background: The management of allergic rhinitis (AR) encompasses education, pharmacotherapy, immunotherapy, and surgery. FK506 (tacrolimus) is an immunosuppressant that inhibits allergic reactions. The purpose of this study was to reveal whether FK506 treatment reduces allergic inflammation in an AR mouse model and to elucidate the mechanisms.

Methods: Forty mice were divided into four groups: control, AR, FK (FK506), and dexamethasone (DEX). All mice except for the control group were sensitized by an i.p. injection of ovalbumin (OVA). After sensitization, the FK and DEX groups were treated with FK506 and DEX intranasally. All sensitized mice were challenged intranasally with OVA. Allergic symptoms and tissue eosinophil counts were recorded. Interleukin (IL)-5, interferon gamma, and IL-10 levels in nasal lavage fluid (NALF) and serum OVA-specific IgE levels were measured. T-bet, GATA-3, and Foxp3 mRNA expression in splenic mononuclear cells were determined by real-time polymerase chain reaction.

Results: In the FK group and DEX group, allergic symptoms, serum OVA-specific IgE, tissue eosinophil counts, IL-5 in NALF, and GATA-3 mRNAs expression decreased (p < 0.05), and IL-10 in NALF and Foxp3 mRNAs expression increased compared with the AR group (p < 0.05). No significant difference was observed between the FK group and the DEX group.

Conclusion: These results suggest that topical FK506 may reduce allergic inflammation and have potency equal to DEX in the AR model. This mechanism may involve not only Th2 cells but also regulatory T cells. Additional studies are needed on FK506, but in the future, we can consider FK506 as an alternative to topical steroids in the treatment of AR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / administration & dosage
  • Allergens / adverse effects
  • Animals
  • Cell Count
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease Models, Animal
  • Eosinophils / pathology
  • Female
  • Humans
  • Immunization
  • Immunoglobulin E / blood
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / adverse effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism*
  • Leukocytes, Mononuclear / pathology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / administration & dosage
  • Rhinitis, Allergic, Perennial / chemically induced
  • Rhinitis, Allergic, Perennial / diagnosis
  • Rhinitis, Allergic, Perennial / drug therapy*
  • Rhinitis, Allergic, Perennial / immunology*
  • Tacrolimus / administration & dosage*
  • Tacrolimus / adverse effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Allergens
  • Cytokines
  • Immunosuppressive Agents
  • Transcription Factors
  • Immunoglobulin E
  • Dexamethasone
  • Ovalbumin
  • Tacrolimus