Effect of Etanercept Concentration on Human Islet Integrity

Area of Science:

• Transplantation immunology
• Islet cell biology
• Pharmacology

Background:

• Etanercept is an anti-inflammatory drug used in islet transplantation.
• Limited data exists on etanercept's detrimental effects on islets.
• This study aimed to determine the toxic range of etanercept for human islets.

Purpose of the Study:

• To define the toxic range of etanercept for isolated human islets.
• To assess the impact of etanercept on islet yield, purity, viability, and function.
• To guide dosage and administration of etanercept in islet transplantation.

Main Methods:

• Human islets from 8 donors were cultured with etanercept (2.5–40 μg/mL).
• Assessed islet equivalent (IEQ) yield, fragmentation, purity, and viability.
• Measured stimulated insulin release at varying etanercept concentrations.

Main Results:

• Optimal islet yield and viability occurred at 5 μg/mL etanercept.
• Islet loss and fragmentation increased significantly at etanercept concentrations ≥10 μg/mL.
• Insulin secretion was not affected by etanercept ≤10 μg/mL.

Conclusions:

• Etanercept is tolerated by isolated human islets at concentrations <10 μg/mL.
• Higher concentrations (≥10 μg/mL) lead to significant islet damage.
• Consider the narrow therapeutic window for etanercept dosage in islet transplantation.