Leukemia inhibitory factor is immunomodulatory

Abstract

Leukemia inhibitory factor (LIF) is produced by infiltrating immune cells and glial cells during auto-immune and injury responses in the central nervous system (CNS). During these responses, LIF promotes survival of glial cells and neurons. While various studies indicate that LIF also modulates ongoing inflammatory responses in vivo, data on underlying events are lacking. In this study we demonstrate that LIF modulates macrophage function by inhibiting the production of oxygen radicals and TNF-α, both potent mediators of CNS injury in neuroinflammatory diseases such as multiple sclerosis. These immunomodulatory effects of LIF on macrophages are accompanied by activation of the JAK/STAT3 signalling pathway, without affecting AKT and ERK activation. We furthermore show that LIF plays a role in myelin phagocytosis as it stimulates myelin uptake by macrophages. These results demonstrate that LIF has anti-inflammatory properties and enhances myelin clearance, implicating it is an important factor in inflammatory diseases of the CNS.

Publication appears at doi: 10.1016/j.jneuroim.2008.04.005