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Clinical & Experimental Allergy

Effects of long-term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma

Authors


Dr Sly TVW Telethon Institute for Child Health Research, PO Box 855, West Perth 6872, Western Australia.

Abstract

Background

Short-term treatment with leflunomide is effective in suppressing antigen-specific antibody production and allergen-induced bronchoconstriction after sensitization. This agent may thus have a role in future primary prevention strategies in allergic disease.

Objective

The current study aimed to determine whether long-term oral treatment with leflunomide prevents allergic sensitization permanently.

Methods

After sensitization with ovalbumin, six groups of rats (n = 31) were treated daily with leflunomide or diluent for up to 30 days. Ovalbumin-specific IgE and IgG were determined weekly for at least 2 weeks after cessation of treatment. T lymphocytes from another 21 animals were stimulated ex vivo with ovalbumin or concanavalin A.

Results

Ovalbumin-specific IgE and IgG were lower during treatment with leflunomide compared with controls (P < 0.002) but increased after the cessation of treatment. Antigen-specific T-cell proliferation was decreased in cells obtained from leflunomide treated animals (P < 0.05), but not when stimulated with concanavalin A. Eosinophil (P < 0.0001) and neutrophil (P < 0.02) numbers in bronchoalveolar lavage 24 h after allergen challenge were lower in the leflunomide treated animals.

Conclusions

Leflunomide prevents antigen-specific immunoglobulin production after sensitization during treatment, inhibits allergen-induced airway inflammation and diminishes antigen-specific T lymphocyte proliferation.

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