Harnessing the benefits of neuroinflammation: Generation of macrophages/microglia with remarkable remyelinating properties

Excessive inflammation within the central nervous system is injurious, but an immune response is also required for its repair. Macrophages are versatile cells that adopt different properties depending upon their microenvironment. Exposing macrophages to interleukin-4 and -13 (IL4/IL13) has incurred interest for their reparative properties. Unexpectedly, while macrophages exposed to the classic pro-inflammatory signals (interferon-γ/lipopolysaccharide, IFN/LPS) killed neurons and oligodendrocytes in culture, the addition of LPS to IL4/IL13-treated macrophages profoundly elevated IL10, repair metabolites (lactate, ornithine), glucose metabolism and the oligodendrocyte-trophic heparin-binding epidermal growth factor (HBEGF); cells did not display pro-inflammatory or neurotoxic features. We subjected activated murine bone marrow derived macrophages (BMDMs) to microarray analysis to identify activation states of cells. To determine the signature gene expression, BMDMs were treated with IFN gamma/LPS, IL4/IL13 and LPS/IL4/IL13 for 6h and subjected to microarray analysis. Two (2) controls and 2 treatments (cytokines treated) samples were generated from BMDMs. Thus, a total of 8 RNA samples from activated BMDMs were obtained for microarray analysis.