title: Immunologically induced electrophysiological dysfunction: implications for inflammatory diseases of the CNS and PNS.
abstract: During inflammation of the central or peripheral nervous system, a high number of immunologically active molecules, including bacterial or viral products as well as host-derived cytokines, are released. Patients suffering from inflammatory CNS or PNS diseases often develop transient symptoms with a rapid recovery, which obviously cannot be accounted for by immunologically induced tissue damage. These observations led to the hypothesis that immunologically active molecules can affect directly the electrophysiological functions of neurons and glial cells. Evidence for this hypothesis came from in vitro studies showing that cytokines, such as interleukins or tumor necrosis factors, arachidonic acid and its metabolites, interfere with electrophysiological properties of neurons or glial cells. These molecules affect ion currents, intracellular Ca2+ homeostasis, membrane potentials, and suppress or enhance the induction and maintenance of long-term potentiation. Similarly, virus proteins from human immunodeficiency virus type I were found to alter intracellular Ca2+ concentrations of neurons and astrocytes by modulating either transmitter receptors and channels or membrane transporters. Cerebrospinal fluid from MS patients contains factors which increase Na+ current inactivation and thereby reduce neuronal excitability. Immunoglobulins in sera of patients suffering from multifocal motor neuropathy and from acquired neuromyotonia interfere with nerve fibers, inducing alterations of conduction. Increased knowledge of these mechanisms will help to explain the pathogenesis of neurological symptoms and may provide a rationale for new therapeutic strategies.
authors.affiliation: Department of Neurology, Heinrich-Heine University Düsseldorf, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Köller
authors.forename: M
authors.initials: M
authors.lastname: Siebler
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D001424:Bacterial Infections / Q000276:immunology / Q000503:physiopathology; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000503:physiopathology*; D004594:Electrophysiology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000821:virology; D010523:Peripheral Nervous System Diseases / Q000276:immunology* / Q000503:physiopathology*; D014777:Virus Diseases / Q000276:immunology / Q000503:physiopathology