Interleukin-1β differentially affects interleukin-6 and soluble interleukin-6 receptor in the blood and central nervous system of the monkey

Two studies were conducted to investigate whether behavioral and physiological responses induced by administration of interleukin-1β (IL-1β) were also associated with changes in interleukin-6 (IL-6) and soluble IL-6 receptor levels (sIL-6R). Following intravenous injection of rhIL-1β, blood arid cerebrospinal fluid (CSF) samples were collected from juvenile rhesus monkeys. Marked increases in IL-6 levels were evident at 1 h in both blood and intrathecal compartments. IL-1β also induced significant elevations in the release of ACTH and cortisol into the blood stream, and following high doses, the monkeys evinced signs of sickness behavior. The second study characterized the IL-1β dose-response relationship showing that these physiological changes were most evident at doses between 0.5 μg and 1.0 μg IL-1/kg body weight. Soluble IL-6 receptor concentration was also increased, but only in plasma. There was no detectable sIL-6R in CSF. The large release of IL-6 into CSF suggests that some behavioral symptoms may be due to intrinsic changes in central nervous system activity concomitant with the alterations in peripheral physiology.