CNS Cytokines

Abstract

The first description of the inflammatory process appeared as early asthe first century AD. Among the first things learned about inflammationis that vascular permeability is increased and leukocyte extravasationoccurs. It is now realized that the central nervous system (CNS) is notas devoid of immune cell entrance as once believed and thatneuroinflammation can occur. Even in the CNS absence of peripheralimmune cells, cytokines from the periphery can influence glialactivation in response to endogenous or exogenous stresses. Activatedglial cells will secrete proinflammatory cytokines among other factors.The presence of relatively high concentrations of proinflammatorycytokines, such as IL-1, IL-6, and TNF-alpha, in the brain producessickness behavior. Neuroinflammation is not only caused by viral orbacterial infection, but can also be the result of physical injury orneurodegenerative diseases, such as Alzheimer's disease, Parkinson'sdisease, multiple sclerosis, and cerebral palsy. This chronicneuroinflammation is associated with a number of common factors; mostnotable among these is the increased concentration of proinflammatorycytokines. In addition to the ones listed above, others have beendetected including, IL-18, IL-33, and HMGB I. Although TGF-beta 1functions most often as an anti-inflammatory cytokine, under certaincircumstances it, too, can have proinflammatory activity. Other commonfeatures of neuroinflammation include increased production of reactiveoxygen species (ROS) and nitric oxide (NO), which function to increaseapoptosis and promote neuronal damage. Activation of astrocytes isdetected by elevated GFAP expression. Activated astrocytes promotechemokine expression causing permeability of the blood brain barrier(BBB), thus allowing leukocytes to enter the brain tissue. The heavymetal Pb accumulates in glial cells and in doing so can potentiatecytokine and glutamate-mediated increases in the BBB permeability, aswell as cause chronic glial cell activation. Pb's ability to promotegliosis and deficiencies in chaperone protein function has prompted acomparison of Pb toxicity to certain neurodegenerative disorders, suchas Alzheimer's and Parkinson's diseases. Toxicity of other metals, suchas, Al, Cu, Cd, Zn, and Hg was also found to share common features withAlzheimer's disease.