Therapeutic effects of combination using glucosamine plus tacrolimus (FK-506) on the development of atopic dermatitis-like skin lesions in NC/Nga mice

Scand J Immunol. 2012 May;75(5):471-8. doi: 10.1111/j.1365-3083.2011.02659.x.

Abstract

Tacrolimus (FK-506) has been found to exhibit potent inhibitory effects on spontaneously developed dermatitis. We previously showed that glucosamine prevents the development of Atopic dermatitis (AD)-like skin lesions in NC/Nga mice. The aims of our study were to investigate the synergistic therapeutic efficacy of combination of glucosamine plus FK-506 in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 8 were used for treatment with glucosamine (500 mg/kg) alone, FK-506 (1.0 mg/kg) or in combination. The synergistic effects of combination therapy were evaluated by dermatitis scores, skin histology and immunological parameters such as IgE, Th2-mediated cytokines and chemokines, CD3(+) T cells and CLA(+) T cells. Combined therapy using glucosamine plus FK-506 improved the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores. The suppression of dermatitis by combined therapy was accompanied by a decrease in the plasma level of IgE and in the splenic level of IL-5, IL-13, TARC and eotaxin. Histological finding indicated that the dermal infiltration of inflammatory cells including mast cells and eosinophils was greatly reduced. Particularly, immunohistological evaluation reveals a reduction in CD3(+) T cells and CLA(+) cells in the combined therapy. Our findings suggest that combination therapy of glucosamine plus FK-506 was more synergistic efficacy than single-modality treatment with either alone to improve the development of established dermatitis in NC/Nga mice model. This combined immunosuppressive therapy may provide an effective therapeutic strategy for the treatment of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / biosynthesis
  • Chemokine CCL11 / biosynthesis
  • Chemokine CCL17 / biosynthesis
  • Chemokines / biosynthesis
  • Cytokines / biosynthesis
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Dermatitis, Atopic / prevention & control
  • Dermatophagoides farinae / immunology*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Glucosamine / pharmacology
  • Glucosamine / therapeutic use*
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin E / blood
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Interleukin-13 / biosynthesis
  • Interleukin-5 / biosynthesis
  • Male
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mice
  • Scavenger Receptors, Class B / biosynthesis
  • Skin / drug effects
  • Skin / immunology
  • Skin / pathology
  • Tacrolimus / pharmacology*
  • Tacrolimus / therapeutic use*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • CD3 Complex
  • Ccl11 protein, mouse
  • Ccl17 protein, mouse
  • Chemokine CCL11
  • Chemokine CCL17
  • Chemokines
  • Cytokines
  • Immunosuppressive Agents
  • Interleukin-13
  • Interleukin-5
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B
  • Immunoglobulin E
  • Glucosamine
  • Tacrolimus