Oral Administration of Leflunomide (HWA486) Results in Prominent Suppression of Immunoglobulin E Formation in a Rat Type 1 Allergy Model
Leflunomide, a drug being developed for use in the treatment of rheumatoid arthritis, was evaluated in an ovalbumin (OVA)-induced rat type 1 allergy model. In a dose of 1 mg/kg/day, it strongly suppressed the formation of OVA-specific IgE, thus preventing the elevation of the plasma histamine level...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 288; no. 2; pp. 849 - 857 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.02.1999
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Subjects | |
Online Access | Get full text |
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Summary: | Leflunomide, a drug being developed for use in the treatment of rheumatoid arthritis, was evaluated in an ovalbumin (OVA)-induced
rat type 1 allergy model. In a dose of 1 mg/kg/day, it strongly suppressed the formation of OVA-specific IgE, thus preventing
the elevation of the plasma histamine level and induction of anaphylactic shock observed after i.v. challenge with OVA. Studies
on leflunomideâs effects on the secondary antibody response showed that administration during the primary immune response
remarkably diminished the secondary antibody responses, except IgM, even without further drug administration. Furthermore,
when administered during the secondary response after rechallenge, both the total IgE and OVA-specific IgE serum levels declined
rapidly to nearly baseline levels. Although OVA-specific IgG1, IgG2a, and IgM did not decrease from their primary response
levels, these classesâ secondary responses were strongly suppressed. In an in vitro study, the proliferation and antibody
production of OVA-stimulated spleen cells, derived from Brown Norway rats, were strongly inhibited by A77 1726 , leflunomideâs active metabolite. When uridine was added to the cell culture, this moleculeâs effect on cell proliferation
was completely restored, whereas the antibody production was partially restored. These findings are consistent with data indicating
that leflunomide is a dihydroorotate dehydrogenase inhibitor. Taken together, the above findings suggest the therapeutic potential
of leflunomide against type 1 allergic diseases. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3565 1521-0103 |