Alcohol-induced gastritis prevents oral tolerance induction in mice
Alcohol-induced gastritis prevents oral tolerance induction in mice
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DOI：
10.1111/j.1365-2249.2006.03207.x
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发表时间：
2006-11-01
影响因子：
4.6
通讯作者：
Faria, A. M. C.
中科院分区：
文献类型：
--
作者：
Andrade, M. C.;Menezes, J. S.;Faria, A. M. C.
尽管有一些关于炎症性肠病与肠道免疫调节机制之间的免疫学关系的报道，但针对胃粘膜炎症过程对口服耐受等事件影响的系统研究仍然有限。在此，我们报告建立了一种短期施用乙醇诱导的新型小鼠胃炎模型。描述了该临床实体的主要免疫学特征及其对诱导口服耐受的影响。我们的数据表明，连续 4 天摄入乙醇会引发胃部急性炎症反应，称为乙醇诱发性胃炎，其特征为充血、水肿和混合单核/多形核细胞浸润。除了局部免疫学变化，例如高水平的胃白细胞介素 (IL)-4 和干扰素 (IFN)-γ，还观察到全身变化，包括 IL-4 合成增加、血清 IgE 水平升高以及脾细胞不产生 IL-10。此外，乙醇诱导的胃炎可阻止卵清蛋白（OVA）口服耐受的诱导，治疗动物中抗 OVA 体液和细胞免疫反应未改变就证明了这一点。 OVA 足垫免疫后组织嗜酸性粒细胞增多表明口服乙醇治疗可诱导过敏型反应。综上所述，我们的研究结果表明，短期乙醇摄入与胃炎症事件有关，胃炎症事件能够破坏维持粘膜稳态和口服耐受的免疫调节机制。
Despite several reports on the immunological relationship between inflammatory bowel diseases and immunoregulatory mechanisms in the gut, systematic studies addressing the impact of inflammatory processes in the gastric mucosa on events, such as oral tolerance, are still limited. Herein, we report the establishment of a novel murine model of gastritis induced by short-term administration of ethanol. The major immumological features of this clinical entity are characterized, as well as its impact on the induction of oral tolerance. Our data demonstrate that ethanol ingestion during 4 consecutive days triggered an acute inflammatory reaction in the stomach referred as ethanol-induced gastritis and characterized by hyperaemia, oedema and mixed mononuclear/polymorphonuclear cell infiltrate. Besides local immunological changes, such as high levels of gastric interleukin (IL)-4 and interferon (IFN)-gamma, systemic alterations are also observed, including increased IL-4 synthesis, enhanced levels of serum IgE and absence of IL-10 production by spleen cells. Moreover, ethanol-induced gastritis prevents oral tolerance induction to ovalbumin (OVA) as demonstrated by unaltered anti-OVA humoral and cellular immune responses in treated animals. Tissue eosinophilia after footpad immunization with OVA suggests that oral treatment with ethanol induced an allergic-type reaction. Taken together, our findings indicate that short-term ethanol ingestion is associated with gastric inflammatory events able to break immunoregulatory mechanisms that maintain mucosal homeostasis and oral tolerance.