Lymph node transplantation is a promising surgical technique for the treatment of lymphedema. However, while initial clinical results have been largely promising, inconsistent responses have been reported in some cases. While the cause of this inconsistency remains unknown, it is likely that impaired lymphangiogenesis and spontaneous regeneration of lymphatic vessels in the transplanted lymph nodes may be a contributing factor suggesting that development of novel techniques to augment lymphangiogenesis may be clinically useful. The aim of this study was therefore to determine if sterile inflammatory reactions can serve as a physiologic means of augmenting lymphangiogenesis in transplanted lymph nodes using a murine model.

We used our previously reported model of lymph node transfer to study the effect of sterile inflammation on lymphatic regeneration. Mice were divided into 3 groups: Group 1 animals served as controls and underwent lymphadenectomy followed by immediate lymph node transplantation without inflammation. Group 2 animals (inflammation before transfer) were transplanted with lymph nodes harvested from donor animals in which a sterile inflammatory reaction was induced in the ipsilateral donor limb using complete Freund’s adjuvant and ovalbumin (CFA/OVA). Group 3 animals (inflammation after transfer) were transplanted with lymph nodes and then inflammation was induced in the ipsilateral limb using CFA/OVA. Lymphatic function, lymphangiogenesis, and lymph node histology were examined 28 days after transplant and compared with normal lymph node.

Animals that had sterile inflammation after transplantation (group 3) had significantly improved lymphatic function (>2 fold increase) as assessed by lymphoscintigraphy, increased peri-nodal lymphangiogenesis, and functional lymphatics as compared with no-inflammation or inflammation before transplant groups (p<0.01). In addition, inflammation after transplantation was associated a more normal lymph node architecture, expansion of B cell zones, and decreased percentage of T cells as compared with the other experimental groups.

Sterile inflammation is a potent method of augmenting lymphatic function and lymphangiogenesis after lymph node transplantation and is associated with maintenance of lymph node architecture. Induction of inflammation after transplant is the most effective method and promotes maintenance of normal lymph node B and T cell architecture.