INDUCTION OF INTERLEUKIN-1 IN VARIOUS BRAIN-REGIONS AFTER PERIPHERAL AND CENTRAL INJECTIONS OF LIPOPOLYSACCHARIDE

The presence of bioactive interleukin-l (IL-1) in various brain region s (cerebellum, cortex, brainstem, diencephalon or hippocampus) after e ither intraperitoneal (i.p.) or intraventricular (i.c.v.) injection of lipopolysaccharide (LPS) was studied in the rat. To detect IL-1, extr acellular fluid and cell lysate were fractionated by gel exclusion chr omatography and fractions tested for thymocyte stimulation; presence o f IL-1 was confirmed by blockade of stimulation by addition to the ass ay of a monoclonal antibody (mAb) to IL-1 receptor. When LPS was infus ed i.c.v., IL-1 was detected in the brainstem and diencephalon 2 h aft er injection, and in all the brain regions except cerebellum 6 h after injection; IL-1 was not detected in the plasma of these animals. When LPS was injected i.p., IL-1 was detected in the plasma but not in the brain 2 h after the injection, and in all brain regions but not in th e plasma 6 h after the injection. In all of these cases, IL-1 was foun d in extracellular fluid; in some cases (cortex, cerebellum) cell lysa te of the region did not produce detectable bioactivity, thereby indic ating that IL-1 in these brain regions is processed to active peptide during release, as has been reported in the periphery. In those cases where bioactivity was detected in cell lysate (brainstem, diencephalon ), bioactivity was not blocked by IL-1 receptor mAb, indicating presen ce of a non-IL-l stimulating factor. These results further support the idea that IL-1 is secreted by cells in the brain, and indicate that i t is found in the extracellular fluid of many brain regions following an appropriate stimulus in the periphery as well as in the brain.