LIPOPOLYSACCHARIDES AND LEUKOTRIENE B4 INDUCE INDEPENDENTLY REGULATEDELECTROPHYSIOLOGICAL AND IMMUNOLOGICAL RESPONSES IN CULTURED ASTROCYTES

Astrocytes play an important role in immunological processes within th e central nervous system. They are able to produce cytokines like inte rleukin 6 (IL-6) and depolarize substantially after stimulation by lip opolysaccharides (LPS) or leukotriene B-4 (LTB(4)). Therefore, we inve stigated the coupling between these immunological and electrophysiolog ical processes. Amiloride (250 mu M), a blocker of various Na+ transpo rt systems, inhibited LPS (5 mu g/ml)-induced depolarization, whereas the LPS-induced release of IL-6 was unaffected, indicating different i ntracellular regulatory mechanisms. LTB(4) (1.0 mu M) induced a depola rization of a similar degree but mediated by a different ionic mechani sm and failed to induce a detectable IL-6 release. Dexamethasone (1.0 mu M) and cycloheximide (2.0 mu M) specifically reduced LTB(4)-induced depolarization, while LPS-induced depolarization was unaffected, prov iding further evidence for different regulatory pathways. Neither the depolarization nor the immunological stimuli served as a proliferation signal. These data demonstrate that independent immunological and ele ctrophysiological responses with specific intracellular regulation are evoked after stimulation with LPS or LTB(4). With respect to function al disturbance of depolarized glial cells, e.g. in maintaining local i onic homeostasis, neuronal excitability may be affected indirectly and by this way account for the appearance of neurological symptoms durin g inflammatory CNS diseases.