Proinflammatory and antiinflammatory cytokines in multiple sclerosis and central nervous system acquired immunodeficiency syndrome.
While certain cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), IL-6, and transforming growth factor-beta (TGF-beta) may be involved in pro- and anti-inflammatory events in the central nervous system (CNS) of patients with multiple sclerosis (MS) and CNS acquired immunodeficiency syndrome (AIDS), there is not uniform consensus as to whether they are elevated or even detectable in all compartments of the body such as serum, cerebrospinal fluid (CSF), and tissue. Furthermore, if they are elevated in these diseases, there are no data as to whether they regulate the disease process itself. Myelin damage in MS is a punctate demyelination; in AIDS, it is a diffuse myelin pallor or dysmyelination. Oligodendrocytes are destroyed in MS but not CNS AIDS, suggesting a different mechanism for myelin loss in the two diseases. These different pathologies may provide clues about the role of macrophages, microglia, and/or the toxic products they produce in putatively giving rise to myelin damage. The stimuli that trigger such a destructive response by macrophages or glial cells and/or the regulation of the toxic events in the two diseases we would predict to be different. In MS, an effector cell-mediated lesion production and oligodendrocyte cell destruction seem to occur. We hypothesize that the effector is the inflammatory blood macrophage and/or microglial cell induced and promoted to its cytotoxic activity by a collaboration of neurotransmitters and cytokines. In CNS AIDS, virus-induced toxic products of glia and their diffusion through white and gray matter areas of the brain have been suggested. Such soluble mediators would then compromise metabolic processes of neurons and glia without widespread target cell loss.
Merrill
J E
JE
Department of Neurology, Reed Neurological Research Center, UCLA School of Medicine 90024.
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003711:Demyelinating Diseases / Q000276:immunology; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology*
D016207:Cytokines