Ex vivo intranodal administration of sirolimus

Abstract

Background: Immune-mediated adverse effects of current systemic immunosuppression therapy compromise long-term survival of liver transplant recipients. Our recently observed results showed that intranodal delivery of sirolimus induced interleukin (IL)-10-driven CD4+ CD25+ Foxp3+ regulatory T cells. The present report investigated the feasibility of intra-nodal delivery of sirolimus ex vivo into a human liver common bile duct lymph node.

Methods: We used a discarded donor human liver to directly administer sirolimus into a distal common bile duct lymph node. Sirolimus was injected once using an ultrasound-guided method.

Results: The porta hepatis and its lymph node along the distal common bile duct were exposed. A handheld ultrasound probe (L15-7io, Koninklijke Philips N.V.) with a layer of standoff Aquasonic 100 Ultrasound Transmission Gel (Parker Laboratories, Inc) was applied to the exposed lymph node. Using a 1.0-mL 25G hypodermic needle, 0.05 mL of sirolimus solution was injected directly into the exposed lymph node.

Conclusions: Under sonographic guidance, direct injection of sirolimus into a hepatic draining lymph node along the common bile duct is accomplished precisely and reliably. Direct administration of therapeutic agents into local lymph nodes is a viable approach for effective targeted immunotherapy.

Keywords: Immunosuppression; Liver transplant; Lymph nodes; Sirolimus.