| First Author | Brandt EB | Year | 2009 |
| Journal | J Allergy Clin Immunol | Volume | 123 |
| Issue | 1 | Pages | 53-8 |
| PubMed ID | 18996576 | Mgi Jnum | J:296566 |
| Mgi Id | MGI:6460137 | Doi | 10.1016/j.jaci.2008.10.001 |
| Citation | Brandt EB, et al. (2009) Targeting IL-4/IL-13 signaling to alleviate oral allergen-induced diarrhea. J Allergy Clin Immunol 123(1):53-8 |
| abstractText | BACKGROUND: Intestinal anaphylaxis (manifested by acute diarrhea) is dependent on IgE and mast cells. OBJECTIVE: We aimed to define the respective roles of IL-4 and IL-13 and their receptors in disease pathogenesis. METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
