α1-Antitrypsin Therapy Downregulates Toll-Like Receptor-Induced IL-1β Responses in Monocytes and Myeloid Dendritic Cells and May Improve Islet Function in Recently Diagnosed Patients With Type 1 Diabetes Academic Article uri icon

abstract

  • Context: Recent studies have implicated proinflammatory responses in the mechanism of type 1 diabetes (T1D). Objective: Our objective was to evaluate the safety and effects of therapy with the anti-inflammatory serum protein α1-antitrypsin (AAT) on islet function and innate immunity in recent-onset patients. Design and Setting: This was an open-label phase I trial at the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver. Patients: Twelve recently diagnosed subjects with T1D with detectable C-peptides were included in the study. Intervention: Eight consecutive weekly infusions of 80 mg/kg of AAT were given. Main Outcome Measures: Patients were monitored for adverse effects of AAT therapy, C-peptide responses to a mixed-meal tolerance test, and toll-like receptor (TLR)-induced cellular IL-1β in monocytes and myeloid dendritic cells (mDCs). Results: No adverse effects were detected. AAT led to increased, unchanged, or moderately reduced levels of C-peptide responses compared with bas...

publication date

  • January 1, 2014