The cytokine leukemia inhibitory factor (LIF) protected against the development of graft vs host disease without affecting graft  vs leukemia (GVL) activity in mice, according to the results of study published in the journal Blood.

The known function of LIF includes pluripotent stem cell self-renewal, maternal reproduction, inflammation, and tumorigenesis. Previous studies also suggest that LIF may modulate the immune response and inflammation through different lymphocytes. The aim of this study was to determine if LIF plays a role in GVHD.

In this study, mice were irradiated and underwent an allogeneic (allo) bone marrow transplant (BMT) with or without T cells. Control mice underwent total body irradiation (TBI) only, received BMT from a syngeneic mouse (syn-BMT), received a BMT from an allogeneic mouse, or were naïve and received no treatment. LIF levels were highest among mice that underwent an allo-BMT followed by mice that underwent TBI or syn-BMT compared with other control mice, and was at its highest level 2 days after treatment.


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Mice that underwent allo-BMT developed GVHD and death within 30 days. However, the administration of rLIF beginning 4 days prior and up to 3 days after the BMT resulted in a significant decrease in GVHD. Mice that received rLIF beginning at 4 days before transplant had longer survival (P <.001), less body weight loss (P <.05), and lower GVHD scores (P <.05) compared with vehicle-treated mice.

Administration of rLIF after irradiation was shown to activate STAT1 signaling, causing downregulation of the expression of interleukin-12-p40 expression in dendritic cells. This resulted in a decrease of major histocompatibility complex II levels expressed by intestinal epithelial cells, and decreased donor T-cell activation and infiltration.

The authors concluded that “our results suggest a potential translational application of LIF as a therapeutic agent to protect against GVHD while preserving GVL.”

Reference

Wang J, Chang C-Y, Yang X, et al. Leukemia inhibitory factor protects against graft-versus-host disease while preserving graft-versus-leukemia activity. Blood. 2022;140:2076-2090. doi: 10.1182/blood.2022015677