Interleukin-l (Il-l) is a well-characterized immunomodulator released by monocytes, macrophage, and microglia. Outside the central nervous system (CNS), this pluripotent monokine has diverse functions as a cell activator, growth factor, and cytotoxin. In the past 2 years we have established the presence of Il-l in the CNS during development and after injury. Using in vitro techniques we have determined that ameboid microglia are a principal source of brain Il-1 and that astroglia are a principal target. We will extend our study of monokines in the CNS by exploring Il-l production in situ after CNS injury and during embryogenesis. We will examine brain mononuclear phagocyte-astroglia relationships in the developing cerebellum and in traumatized cerebrum. To elucidate the regulation of brain Il-1 production we will identify soluble CNS factors that stimulate microglial release of II-1. We will also investigate the presence and actions of membrane-bound Il-l in microglia and study further Il-l as an astrocyte activator. Microinjections into the spinal cord will be used to assess monokine effects on neurologic function. A multidisciplinary approach will be used to execute the proposed research involving such techniques as tissue culture, immuno-histochemistry, protein purification, histology, and neurosurgical procedures. If successful, this proposed research will identify fundamental interactions between the immune and central nervous systems.
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