Leukemia inhibitory factor gene improves skin allograft survival in the mouse model

Leukemia inhibitory factor (LIF) is a widely expressed cytokine involved in both local and systemic immune response. Furthermore, it has been implicated in various immunological processes including thymic T cell maturation and embryo implantation. We investigated implication of various modalities in the application of prolonged and viable allograft to the wound, using cytokines and growth factors.

BALB/c and B6D2F1 strains of mice were used either as a skin graft donor or host. LIF cDNA inserted in plasmid vector or the vector alone was injected intradermally in graft skin and observed up to 21 days. LIF, LIF-receptor, gp130, as well as type 1 and 2 T helper cytokine expressions were investigated by reverse transcription polymerasse chain reaction, in situ hybridization, and histological studies.

LIF cDNA-treated groups showed significantly improved graft survival compared to the vector-treated control in 21 days postoperatively for grafting from B6D2F1 to BALB/c and BALB/c to B6D2F1. LIF and LIF receptor mRNA expressions were observed 24 hr and 21 days posttransplantation. The gp130 expression was only observed in LIF-treated B6D2F1 to BALB/c allografting on day 21 posttransplantation. LIF transcripts were strongly present in the epidermal, dermal, and subdermal tissues as determined by an in situ hybridization of LIF-treated grafting.

These results suggest that LIF cDNA treatment is an effective and beneficial adjuvant for the skin allograft survival. Improved skin allograft modulation by cytokine gene transfer is a potentially promising therapy for temporary large skin coverage.