The β2-adrenergic agonist salbutamol potentiates oral induction of tolerance, suppressing adjuvant arthritis and antigen-specific immunity
The β2-adrenergic agonist salbutamol potentiates oral induction of tolerance, suppressing adjuvant arthritis and antigen-specific immunity
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DOI：
10.4049/jimmunol.169.9.5028
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发表时间：
2002-11-01
影响因子：
4.4
通讯作者：
Heijnen, CJ
中科院分区：
文献类型：
--
作者：
Cobelens, PM;Kavelaars, A;Heijnen, CJ
通过在疾病过程中饲喂自身抗原来治疗自身免疫性疾病的治疗方案迄今为止还不是很成功。体外吧。已表明β-肾上腺素能激动剂抑制促炎细胞因子的产生并上调抗炎细胞因子的产生。我们假设口服 β(2)-肾上腺素能激动剂沙丁胺醇可增强口服 Ag 的保护作用。在此，我们证明口服沙丁胺醇与 Ag 分枝杆菌 65-kDa 热休克蛋白组合可增加大鼠佐剂关节炎中疾病抑制耐受诱导的功效。为了更详细地研究沙丁胺醇的机制，我们还在 BALB/c 小鼠的 OVA 耐受模型中测试了口服沙丁胺醇。 OVA 免疫后口服 OVA/沙丁胺醇可有效抑制对 OVA 的细胞反应和不道德反应。沙丁胺醇的共同给药与肠道中 IL-10、TGF-β 和 IL-1R 拮抗剂的立即增加有关。沙丁胺醇/OVA 的耐受作用维持至少 12 周。此时，OVA/沙丁胺醇治疗的动物中 Ag 刺激的脾细胞中 IFN-γ 的产生增加。总之，沙丁胺醇通过促进口服耐受诱导，对治疗自身免疫性疾病具有巨大的临床益处。
Therapeutic protocols for treating autoimmune diseases by feeding autoantigens during the disease process have not been very successful to date. In vitro it. has been shown that beta-adrenergic agonists inhibit pro-inflammatory cytokine production and up-regulate anti-inflammatory cytokine production. We hypothesized that the protective effect of oral administration of Ag would be enhanced by oral coadministration of the beta(2)-adrenergic agonist salbutamol. Here we demonstrate that oral administration of salbutamol in combination with the Ag mycobacterial 65-kDa heat shock protein increased the efficacy of disease-suppressive tolerance induction in rat adjuvant arthritis. To study the mechanism of salbutamol in more detail, we also tested oral administration of salbutamol in an OVA tolerance model in BALB/c mice. Oral coadministration of OVA/salbutamol after immunization with OVA efficiently suppressed both cellular and Immoral responses to OVA. Coadministration of salbutamol was associated with an immediate increase in IL-10, TGF-beta, and IL-1R antagonist in the intestine. The tolerizing effect of salbutamol/OVA was maintained for at least 12 wk. At this time point IFN-gamma production in Ag-stimulated splenocytes was increased in the OVA/salbutamol-treated animals. In conclusion, salbutamol can be of great clinical benefit for the treatment of autoimmune diseases by promoting oral tolerance induction.