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


CONCLUSIONS
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.
D000485:Allergens / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000917:Antibody Formation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004167:Diphtheria Toxin / Q000494:pharmacology*; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D000922:Immunotoxins / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D010796:Phthalic Anhydrides / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical