Increased Levels of IL-16 in the Central Nervous System during Neuroinflammation Are Associated with Infiltrating Immune Cells and Resident Glial Cells

SIMPLE SUMMARY: Interleukin-16 is a protein involved in the migration of some immune cells and plays an important role in the development of multiple sclerosis, an inflammatory demyelinating disease that affects the central nervous system (i.e., brain and spinal cord). Currently, it is not fully understood which cells produce interleukin-16 during the inflammatory response in the central nervous system. This study investigates the correlation between the expression levels of interleukin-16 and the severity of neuroinflammation and determines the cells which produce interleukin-16, using a mouse model of multiple sclerosis. Our data show that the expression levels of interleukin-16 are significantly increased in the brain and spinal cord tissues of the mouse model compared to controls. Furthermore, other immune assays reveal that the significantly increased number of cells expressing interleukin-16 in the central nervous system lesions are likely to be infiltrating immune cells and resident glial cells, but not neurons. Our findings suggest that interleukin-16 is closely involved in the pathology of multiple sclerosis and other inflammatory diseases in the central nervous system via the glial and infiltrating immune cells. ABSTRACT: Interleukin (IL)-16, a CD4(+) immune cell specific chemoattractant cytokine, has been shown to be involved in the development of multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). While immune cells such as T cells and macrophages are reported to be the producers of IL-16, the cellular source of IL-16 in the CNS is less clear. This study investigates the correlation of IL-16 expression levels in the CNS with the severity of neuroinflammation and determines the phenotype of cells which produce IL-16 in the CNS of experimental autoimmune encephalomyelitis (EAE) mice. Our data show that IL-16 expression is significantly increased in the brain and spinal cord tissues of EAE mice compared to phosphate buffered saline (PBS) immunised controls. Dual immunofluorescence staining reveals that the significantly increased IL-16(+) cells in the CNS lesions of EAE mice are likely to be the CD45(+) infiltrating immune cells such as CD4(+) or F4/80(+) cells and the CNS resident CD11b(+) microglia and GFAP(+) astrocytes, but not NeuN+ neurons. Our data suggest cytokine IL-16 is closely involved in EAE pathology as evidenced by its increased expression in the glial and infiltrating immune cells, which impacts the recruitment and activation of CD4(+) immune cells in the neuroinflammation.