Distinct structural requirements for interleukin-4 (IL-4) and IL-13 binding to the shared IL-13 receptor facilitate cellular tuning of cytokine responsiveness.

Both interleukin-4 (IL-4) and IL-13 can bind to the shared receptor composed of the IL-4 receptor alpha chain and the IL-13 receptor alpha1 chain (IL-13Ralpha1); however, the mechanisms by which these ligands bind to the receptor chains are different, enabling the principal functions of these ligands to be different. We have previously shown that the N-terminal Ig-like domain in IL-13Ralpha1, called the D1 domain, is the specific and critical binding unit for IL-13. However, it has still remained obscure which amino acid has specific binding capacity to IL-13 and why the D1 domain acts as the binding site for IL-13, but not IL-4. To address these questions, in this study we performed mutational analyses for the D1 domain, combining the structural data to identify the amino acids critical for binding to IL-13. Mutations of Lys-76, Lys-77, or Ile-78 in c' strand in which the crystal structure showed interaction with IL-13, and those of Trp-65 and Ala-79 adjacent to the interacting site, resulted in significant impairment of IL-13 binding, demonstrating that these amino acids generate the binding site. Furthermore, mutations of Val-35, Leu-38, or Val-42 at the N-terminal beta-strand also resulted in loss of IL-13 binding, probably from decreased structural stability. None of the mutations employed here affected IL-4 binding. These results demonstrate that the D1 domain of IL-13Ralpha1 acts as an affinity converter, through direct cytokine interactions, that allows the shared receptor to respond differentially to IL-4 and IL-13.

[A case of successfully treated nifedipine-poisoning].

Calcium antagonists have been prescribed for treatment of hypertension and several other diseases, and the incidence of poisoning involving these agents is increasing. We encountered and successfully treated a case of nifedipine poisoning. The patient was a 52-year-old man who ingested 76 tablets of nifedipine 20 mg while drinking alcohol. He was brought to a clinic and transferred to our emergency department. Since systolic blood pressure on arrival was 110 mmHg, primary care involved gastric lavage, infusion of lactated Ringer solution, and administration of activated charcoal and cathartics. Hypotension subsequently developed and continuous infusion of dobutamine was initiated. Arrhythmia did not appear during the course of treatment, and the patient was discharged after four days.