CNS Cytokines.

The first description of the inflammatory process appeared as early as the first century AD. Among the first things learned about inflammation is that vascular permeability is increased and leukocyte extravasation occurs. It is now realized that the central nervous system (CNS) is not as devoid of immune cell entrance as once believed and that neuroinflammation can occur. Even in the CNS absence of peripheral immune cells, cytokines from the periphery can influence glial activation in response to endogenous or exogenous stresses. Activated glial cells will secrete proinflammatory cytokines among other factors. The presence of relatively high concentrations of proinflammatory cytokines, such as IL-1, IL-6, and TNF-α, in the brain produces sickness behavior. Neuroinflammation is not only caused by viral or bacterial infection, but can also be the result of physical injury or neurodegenerative diseases, such as Alzheimer΄s disease, Parkinson΄s disease, multiple sclerosis, and cerebral palsy. This chronic neuroinflammation is associated with a number of common factors; most notable among these is the increased concentration of proinflammatory cytokines. In addition to the ones listed above, others have been detected including, IL-18, IL-33, and HMGB1. Although TGF-β1 functions most often as an anti-inflammatory cytokine, under certain circumstances it, too, can have proinflammatory activity. Other common features of neuroinflammation include increased production of reactive oxygen species (ROS) and nitric oxide (NO), which function to increase apoptosis and promote neuronal damage. Activation of astrocytes is detected by elevated GFAP expression. Activated astrocytes promote chemokine expression causing permeability of the blood–brain barrier (BBB), thus allowing leukocytes to enter the brain tissue. The heavy metal Pb accumulates in glial cells and in doing so can potentiate cytokine and glutamate-mediated increases in the BBB permeability, as well as cause chronic glial cell activation. Pb΄s ability to promote gliosis and deficiencies in chaperone protein function has prompted a comparison of Pb toxicity to certain neurodegenerative disorders, such as Alzheimer΄s and Parkinson΄s diseases. Toxicity of other metals, such as, Al, Cu, Cd, Zn, and Hg was also found to share common features with Alzheimer΄s disease. [ABSTRACT FROM AUTHOR]