An IL-2-toxin, DAB389IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production

J Allergy Clin Immunol. 1999 May;103(5 Pt 1):843-9. doi: 10.1016/s0091-6749(99)70428-8.

Abstract

Background: Expression of high-affinity IL-2 receptor (IL-2R) on T lymphocytes, key cells in chronic inflammation, is a T-cell activation marker.

Objective: We sought to evaluate the effect of the fusion protein DAB389IL-2, which kills cells bearing IL-2R, on delayed-type hypersensitivity and antibody production in Brown Norway rats sensitized with trimellitic anhydride (TMA).

Methods: DAB389IL-2 (25 micrograms/kg/day) or placebo was administered intraperitoneally for 8 days over the period of sensitization, starting 2 days before sensitization.

Results: The administration of DAB389IL-2 resulted in a one-third reduction in the number of IL-2R-bearing cells and significant weight loss of animals. Delayed-type hypersensitivity, evaluated at 5 weeks after sensitization, was significantly inhibited by treatment with DAB389IL-2. In contrast, production of IgE anti-TMA antibodies after sensitization was increased by treatment with DAB389IL-2. DAB389IL-2 affected neither IgG anti-TMA antibody nor total IgE levels.

Conclusion: These data imply that systemic administration of DAB389IL-2 in Brown Norway rats influences cells that have regulatory effects on the immune system, resulting in a switch from a TH1 to a TH2 type of immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Animals
  • Antibodies / metabolism
  • Antibody Formation / drug effects
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Diphtheria Toxin / pharmacology*
  • Disease Models, Animal
  • Hypersensitivity, Delayed / prevention & control*
  • Immunoglobulin E / immunology*
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / immunology
  • Immunotoxins / pharmacology*
  • Interleukin-2 / pharmacology*
  • Male
  • Phthalic Anhydrides / immunology
  • Rats
  • Rats, Inbred BN
  • Receptors, Interleukin-2 / biosynthesis
  • Recombinant Fusion Proteins / pharmacology
  • Stimulation, Chemical

Substances

  • Allergens
  • Antibodies
  • Diphtheria Toxin
  • Immunoglobulin G
  • Immunotoxins
  • Interleukin-2
  • Phthalic Anhydrides
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • denileukin diftitox
  • Immunoglobulin E
  • trimellitic anhydride