Eber E, Uhlig T, McMenamin C, Sly P D
Division of Clinical Sciences, TVW Telethon Institute for child Health Research, Perth, Western Australia.
Clin Exp Allergy. 1998 Mar;28(3):376-84. doi: 10.1046/j.1365-2222.1998.00240.x.
Leflunomide is a new anti-inflammatory and immunomodulating agent which is showing promise in several immune disorders, especially rheumatoid arthritis. Its activity profile suggests it may be of use in modulating allergic sensitization.
To investigate the effectiveness of leflunomide in preventing the development of allergic sensitization.
Fifty-three brown Norway rats were sensitized by intraperitoneal injection of ovalbumin and adjuvant (ricin) on day 0. To determine the ability of leflunomide to inhibit primary allergic sensitization six rats were treated with A77 1726, the active metabolite of leflunomide, from day 0 through day 5, six were treated from day 5 through day 10, and nine rats acted as controls. On day 14, ovalbumin-specific serum antibody levels and the magnitude of the early-phase airway response (EAR) after inhalation allergen challenge were assessed. To determine the ability of acute topical treatment with leflunomide to inhibit mast cell degranulation, three groups of five animals received either vehicle, 100 microg A77 1726, or 1000 g A77 1726 60 min prior to aerosol allergen challenge. To determine the effects of leflunomide treatment in vivo on mast cell function in vitro, mast cells were obtained by bronchoalveolar lavage from 17 rats (nine treated with leflunomide and eight controls). Allergen-specific and non-specific degranulation (48/80 induced) were studied.
In the leflunomide treated rats both ovalbumin-specific IgE and IgG levels were significantly reduced, and the increases in lung resistance and lung elastance were essentially abolished, compared to those of the control group. Non significant differences were found in any of the parameters between the two leflunomide treated groups. Topical pre-treatment with leflunomide did not prevent the allergen-induced EAR. Treatment with leflunomide in vivo prevented allergen-induced mast cell degranulation in vitro because the mast cells lacked IgE on their surface. Non allergen-specific degranulation was normal and allergen-induced degranulation could be restored by passive sensitization.
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.
来氟米特是一种新型抗炎和免疫调节药物，在多种免疫性疾病尤其是类风湿关节炎中显示出前景。其活性特征表明它可能可用于调节过敏致敏作用。
研究来氟米特预防过敏致敏作用发生的有效性。
53只棕色挪威大鼠于第0天通过腹腔注射卵清蛋白和佐剂（蓖麻毒蛋白）进行致敏。为确定来氟米特抑制初次过敏致敏作用的能力，6只大鼠从第0天至第5天用A77 1726（来氟米特的活性代谢产物）治疗，6只大鼠从第5天至第10天治疗，9只大鼠作为对照。在第14天，评估卵清蛋白特异性血清抗体水平以及吸入变应原激发后早期气道反应（EAR）的程度。为确定来氟米特急性局部治疗抑制肥大细胞脱颗粒的能力，三组每组5只动物在气溶胶变应原激发前60分钟分别给予赋形剂、100μg A77 1726或1000μg A77 1726。为确定来氟米特体内治疗对体外肥大细胞功能的影响，通过支气管肺泡灌洗从17只大鼠（9只接受来氟米特治疗，8只为对照）获取肥大细胞。研究变应原特异性和非特异性脱颗粒（由48/80诱导）情况。
与对照组相比，来氟米特治疗的大鼠中卵清蛋白特异性IgE和IgG水平均显著降低，肺阻力和肺弹性的增加基本被消除。两个来氟米特治疗组之间在任何参数上均未发现显著差异。来氟米特局部预处理未能预防变应原诱导的EAR。来氟米特体内治疗可预防变应原诱导的体外肥大细胞脱颗粒，因为肥大细胞表面缺乏IgE。非变应原特异性脱颗粒正常，变应原诱导的脱颗粒可通过被动致敏恢复。
这些数据表明来氟米特可通过抑制变应原特异性IgE抗体的产生预防初次过敏致敏作用并预防变应原诱导的EAR。有必要在特应性疾病中进行进一步研究。
