Brandt Eric B, Munitz Ariel, Orekov Tatyana, Mingler Melissa K, McBride Melissa, Finkelman Fred D, Rothenberg Marc E
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
J Allergy Clin Immunol. 2009 Jan;123(1):53-8. doi: 10.1016/j.jaci.2008.10.001. Epub 2008 Nov 8.
Intestinal anaphylaxis (manifested by acute diarrhea) is dependent on IgE and mast cells.
We aimed to define the respective roles of IL-4 and IL-13 and their receptors in disease pathogenesis.
Wild-type mice and mice deficient in IL-4, IL-13, and IL-13 receptor (IL-13R) alpha1 (part of the type 2 IL-4 receptor [IL-4R]) were sensitized with ovalbumin (OVA)/aluminum potassium sulfate and subsequently given repeated intragastric OVA exposures. The IL-4R alpha chain was targeted with anti-IL-4R alpha mAb before or after intragastric OVA exposures.
IL4(-/-) (and IL4/IL13(-/-)) mice produced almost no IgE and were highly resistant to OVA-induced diarrhea, whereas allergic diarrhea was only partially impaired in IL13(-/-) and IL13Ralpha1(-/-) mice. IL13Ralpha1-deficient mice had decreased IgE levels, despite having normal baseline IL-4 levels. Intestinal mast cell accumulation and activation also depended mainly on IL-4 and, to a lesser extent, on IL-13. Prophylactic anti-IL-4R alpha mAb treatment, which blocks all IL-4 and IL-13 signaling, suppressed development of allergic diarrhea. However, treatment with anti-IL-4R alpha mAb for 7 days only partially suppressed IgE and did not prevent intestinal diarrhea.
Endogenously produced IL-13 supplements the ability of IL-4 to induce allergic diarrhea by promoting oral allergen sensitization rather than the effector phase of intestinal anaphylaxis.
肠道过敏反应（以急性腹泻为表现）依赖于免疫球蛋白E（IgE）和肥大细胞。
我们旨在明确白细胞介素-4（IL-4）和白细胞介素-13及其受体在疾病发病机制中的各自作用。
用卵清蛋白（OVA）/硫酸铝钾对野生型小鼠以及缺乏IL-4、IL-13和IL-13受体（IL-13R）α1（2型IL-4受体[IL-4R]的一部分）的小鼠进行致敏，随后反复经胃给予OVA。在经胃给予OVA之前或之后，用抗IL-4Rα单克隆抗体靶向IL-4Rα链。
IL4基因敲除小鼠（以及IL4/IL13双基因敲除小鼠）几乎不产生IgE，对OVA诱导的腹泻具有高度抗性，而在IL13基因敲除小鼠和IL13Rα1基因敲除小鼠中，过敏性腹泻仅部分受损。尽管IL13Rα1基因敲除小鼠的基线IL-4水平正常，但其IgE水平降低。肠道肥大细胞的聚集和激活也主要依赖于IL-4，在较小程度上依赖于IL-13。预防性抗IL-4Rα单克隆抗体治疗可阻断所有IL-4和IL-13信号传导，抑制过敏性腹泻的发展。然而，用抗IL-4Rα单克隆抗体治疗7天仅部分抑制IgE，并未预防肠道腹泻。
内源性产生的IL-13通过促进口服过敏原致敏而非肠道过敏反应的效应阶段来补充IL-4诱导过敏性腹泻的能力。
