SOLUBLE INTERLEUKIN-6 (IL-6) RECEPTOR AUGMENTS CENTRAL EFFECTS OF IL-6 IN-VIVO

The pleiotropic cytokine interleukin-6 (IL-6) controls both the periph eral and central components of the acute-phase response. These activit ies are mediated via the IL-6 membrane receptor, but probably also via agonistic soluble IL-6 receptors (sIL-6Rs). In the present study we c onducted dose-response experiments with rats that were intracerebroven tricularly i.c.v.) injected with recombinant human IL-6 and sIL-6R and determined body temperature, locomotor activity, food intake, and wat er consumption using radiotelemetry and continuous recordings of feedi ng and drinking. IL-6 injected i.c.v. at 1, 10, and 100 ng increased b ody temperature and decreased locomotor activity and food intake, but it did not affect water consumption. When 10 ng sIL-6R, which lacked d etectable biological activity, was injected i.c.v. 1 h before 1 ng IL- 6, the central effects of IL-6 were enhanced and prolonged, and this w as not due to endotoxin contamination of the recombinant proteins. Our data suggest that IL-6 plays an important role in the regulation of b ody temperature, general activity, and food intake in sick animals. Mo reover, we have shown for the first time that it is possible to potent iate the effects of a mediator in vivo by administration of the corres ponding receptor, which is a novel pharmacological tool for increasing receptor capacity.