Lipopolysaccharides and leukotriene B4 induce independently regulated electrophysiological and immunological responses in cultured astrocytes.

Astrocytes play an important role in immunological processes within the central nervous system. They are able to produce cytokines like interleukin 6 (IL-6) and depolarize substantially after stimulation by lipopolysaccharides (LPS) or leukotriene B4 (LTB4). Therefore, we investigated the coupling between these immunological and electrophysiological processes. Amiloride (250 microM), a blocker of various Na+ transport systems, inhibited LPS (5 micrograms/ml)-induced depolarization, whereas the LPS-induced release of IL-6 was unaffected, indicating different intracellular regulatory mechanisms. LTB4 (1.0 microM) induced a depolarization of a similar degree but mediated by a different ionic mechanism and failed to induce a detectable IL-6 release. Dexamethasone (1.0 microM) and cycloheximide (2.0 microM) specifically reduced LTB4-induced depolarization, while LPS-induced depolarization was unaffected, providing 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 electrophysiological responses with specific intracellular regulation are evoked after stimulation with LPS or LTB4. With respect to functional disturbance of depolarized glial cells, e.g. in maintaining local ionic homeostasis, neuronal excitability may be affected indirectly and by this way account for the appearance of neurological symptoms during inflammatory CNS diseases.