Oncostatin M is a Potent Inducer of CNS Inflammation

Abstract

The neuropoietic cytokine oncostatin M (OSM) is expressed in MS lesions, but its function during CNS lesion development is unknown. In order to elucidate the effects of OSM in the CNS, we have induced local expression of mouse OSM in the CNS of C57/Bl6 mice by means of lentiviral vectors and compared the effects of OSM to those of local expression of another neurokine family member leukemia inhibitory factor (LIF). We found that at sites of OSM expression, substantial tissue remodelling occurs, the blood-brain barrier (BBB) is disrupted and serum leaks into the CNS parenchyma. Endothelial cells of the BBB showed a dramatic upregulation of adhesion molecules. None of these effects were detected after CNS-directed expression of LIF. Moreover, local expression of OSM in the healthy CNS induced a strong expression of MHCII and attracted large amounts of T-cells and macrophages/microglia to the CNS. Our study indentified OSM as a pathological neurokine with the potential to induce neuroinflammation in the healthy CNS.