An IL-2–toxin, DAB 389 IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production

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 DAB 389 IL-2, which kills cells bearing IL-2R, on delayed-type hypersensitivity and antibody production in Brown Norway rats sensitized with trimellitic anhydride (TMA). Methods: DAB 389 IL-2 (25 μg/kg/day) or placebo was administered intraperitoneally for 8 days over the period of sensitization, starting 2 days before sensitization. Results: The administration of DAB 389 IL-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 DAB 389 IL-2. In contrast, production of IgE anti-TMA antibodies after sensitization was increased by treatment with DAB 389 IL-2. DAB 389 IL-2 affected neither IgG anti-TMA antibody nor total IgE levels. Conclusion: These data imply that systemic administration of DAB 389 IL-2 in Brown Norway rats influences cells that have regulatory effects on the immune system, resulting in a switch from a T H1 to a T H2 type of immune response. (J Allergy Clin Immunol 1999;103:843-9.)