Leflunomide, a novel immunomodulating agent, prevents the development of allergic sensitization in an animal model of allergic asthma

Abstract

These data suggests that leflunomide can prevent primary allergic sensitization and prevent allergen-induced EAR by inhibiting production of allergen-specific IgE antibodies. Further studies in atopic conditions are warranted.

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

“…We have previously shown that during treatment with leflunomide OA‐specific IgE and IgG production are reduced to levels equivalent to those of naive, nonsensitised control animals [ 15]. All isotypes tested of OA‐specific IgG were equally effected whilst total IgG levels were not.…”

“…We have demonstrated here that leflunomide treatment reduces IgE production and therefore, presumably, IgE activation of mast cells. We have previously shown that IgE dependent mast cell degranulation is inhibited in vitro by leflunomide via prevention of synthesis of allergen‐specific IgE [ 15]. Mast cell mediators are also known to have an effect on the integrity of the endothelial barrier through which these cells pass when migrating from the blood stream into the lung.…”

“…In our previous studies [ 15], A77 1726, the primary metabolite of leflunomide, has been shown to be effective in suppressing antigen‐specific antibody production when given for a period of 5 days after sensitization with ovalbumin. In addition, the early phase airway response to allergen challenge (which occurs within minutes after inhalation of antigen and lasts up to 1 h [ 16] was largely diminished in the A77 1726 treated rats, and the sensitization of mast cells in vivo was inhibited in these animals.…”

“…The relevant allergen is presented to the T cells, which then become activated and undergo proliferation. Leflunomide has been shown not to inhibit T cell production of IL‐4 [ 18, 19], but to inhibit the production of antigen‐specific IgE [ 15]. Protein antigens, such as ovalbumin, house dust mite and grass pollens, are T cell dependent and cannot directly activate B cells.…”

A review of immunologic diseases of the dog

“…Leflunomide was developed originally as an anti-inflammatory drug, but was found to be far more active against a wide range of immune disorders in murine models. These models include asthma, SLE, chronic graft versus host disease, autoimmune tubulointerstitial nephritis, anti-basement membrane glomerulonephritis, allergic encephalomyelitis, autoimmune uveitis, and anti-allograft and anti-xenograft rejection (Eber et al, 1998;Waer, 1996;Wennberg et al, 1997;Xu et al, 1997;Yeh et al, 1996Yeh et al, , 1997. The drug significantly decreases disease-specific antibody formation.…”