Previous observations that centrally injected interleukin-1 beta (IL-1 beta) into rabbits induces a sustained rise in cerebrospinal fluid (CSF) Ca2+ concentration ([Ca2+]) as well as fever, prompted us to undertake an in vitro study to corroborate the in vivo results and gain insight as to the source and mechanism of IL-1 beta-induced Ca2+ mobilization. 2.IL-1 beta treatment of rat striatal slices preloaded with 45Ca2+ elicited a rise in spontaneous 45Ca2+ release which was dose-dependent, delayed in onset and of extended duration. At concentrations of 1, 5 and 10 ng ml-1, the 45Ca2+ efflux increased by 6.3 +/- 1.3 (s.e. mean), 33.4 +/- 5.0 and 159 +/- 10.5% respectively. 3. At 1 microgram ml-1, the specific IL-1 receptor antagonist, IRAP, antagonised the effect induced by, 10 ng ml-1 IL-1. 4. Caffeine 10 mM,which failed to release calcium on its won, potentiated IL-1-elicited 45Ca2+ release. 5. Perfusion with a Ca(2+)-free medium obtained by use of excess EGTA (3 mM) or in the presence of the Ca2+ channel blocker, nifedipine (3 x 10(-8 M) abolished the potentiating effect of caffeine without affecting the IL-1-induced 45Ca2+ release. 6. Preincubation of slices for 4 h with Bordetella pertussis toxin (PTX, 1.3 micrograms ml-1) did not change the pattern of Ca2+ efflux in response to IL-1. 7. In conclusion, these data indicate that IL-1 stimulates calcium release from brain tissue by a specific, receptor-mediated mechanism which partly depends on extracellular calcium but does not involve a PTX-sensitive G protein as part of the transducing signal.
