Clinical improvement and immunohistochemical findings in severe atopic dermatitis treated with interferon gamma

J Am Acad Dermatol. 2000 Jun;42(6):1033-40.

Abstract

Background: Several clinical studies have focused on the therapeutic effects of interferon gamma (IFN-gamma) in patients with severe atopic dermatitis (AD), although the dosage of recombinant IFN-gamma (rIFN-gamma), therapeutic schedule, and the degree of clinical improvement were different among studies. Although the exact mechanism of action of IFN-gamma therapy in AD is not clear, the beneficial effects of IFN-gamma have been attributed mainly to an immunomodulating effect on the expression of certain immunologic markers.

Objective: Our purpose was to study the therapeutic effect of two different dosages of rIFN-gamma on AD and to investigate the change of lesional expression of infiltrating inflammatory cell markers associated with rIFN-gamma therapeutic efficacy.

Methods: Fifty-one patients with severe recalcitrant AD were treated with rIFN-gamma. Twenty patients were treated with 0.5 x 10(6) IU/m(2) of rIFN-gamma (low-dose [LD] group); 21 patients received 1.5 x 10(6) IU/m(2) of rIFN-gamma (high-dose [HD] group); and 10 patients received placebo. The patients were injected subcutaneously 3 times a week for 12 weeks. Immunohistochemical study was performed in 20 patients of the HD group in the initial visit and after completion of rIFN-gamma therapy with a panel of 14 monoclonal antibodies as markers of inflammatory cells and cytokines.

Results: The disease severity of the 2 groups treated with rIFN-gamma was reduced significantly at the end of treatment compared with that of the placebo group (P<.05). More rapid clinical improvement and more effective treatment outcome were seen in the HD group than in the LD group for the initial 6-week treatment period; however, the clinical improvement in both of the treated groups was stable and maintained after week 8 of treatment. Immunohistochemical findings showed statistically significant reduction in the lesional expression of CD25 and EG2 cells that infiltrated into skin after rIFN-gamma therapy.

Conclusion: This study demonstrated that rIFN-gamma therapy for AD is safe and effective. In the early phase of therapy, a higher dosage of rIFN-gamma is more effective; and for the maintenance of clinical improvement, a lower dosage of rIFN-gamma is recommended when high cost and effectiveness of rIFN-gamma are considered. The therapeutic efficacy of rIFN-gamma in AD might be in part related to the decreased number of CD25(+) and EG2(+) inflammatory cells infiltrated into skin.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers / analysis
  • Cost-Benefit Analysis
  • Cytokines / analysis
  • Dermatitis, Atopic / drug therapy*
  • Dermatitis, Atopic / immunology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / therapeutic use*
  • Lymphocytes / immunology
  • Male
  • Receptors, Interleukin-2 / analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Cytokines
  • Receptors, Interleukin-2
  • Interferon-gamma