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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS023113-04
Application #
3406259
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-07-01
Project End
1994-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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Giulian, D; Young, D G; Woodward, J et al. (1988) Interleukin-1 is an astroglial growth factor in the developing brain. J Neurosci 8:709-14
Lachman, L B; Brown, D C; Dinarello, C A (1987) Growth-promoting effect of recombinant interleukin 1 and tumor necrosis factor for a human astrocytoma cell line. J Immunol 138:2913-6
Giulian, D (1987) Ameboid microglia as effectors of inflammation in the central nervous system. J Neurosci Res 18:155-71, 132-3

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