Effects of long-term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma.
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.
Uhlig
T
T
Division of Clinical Sciences, TVW Telethon Institute for Child Health Research, West Perth, Western Australia.
Cooper
D
D
Eber
E
E
McMenamin
C
C
Wildhaber
J H
JH
Sly
P D
PD
D000280:Administration, Inhalation; D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000918:Antibody Specificity / Q000187:drug effects; D001249:Asthma / Q000097:blood / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007555:Isoxazoles / Q000008:administration & dosage* / Q000494:pharmacology; D000077339:Leflunomide; D008297:Male; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000187:drug effects*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D007074:Immunoglobulin G; D007555:Isoxazoles; D007073:Immunoglobulin E; D010047:Ovalbumin; D000077339:Leflunomide