Biological activity and brain actions of recombinant rat interleukin-1α and interleukin-1β

IL-1α and IL-1β have potent effects on the central nervous system resulting in fever, activation of the hypothalamic-pituitary-adrenal axis and behavioural depression. These effects have mainly been studied in rats, using recombinant human and mouse IL-1. Because IL-1α and IL-1β show some species specificity in the potency of their biological activities, the objective of the present work was to directly compare the effects of recombinant rat IL-1α and IL-1β in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1α and IL-1β bound with the same affinity as human IL-1 to the rat insulinoma Rin m5F cell line that mainly expresses type I IL-1 receptors. This binding activated IL-1 receptors, as shown by induction of the synthesis of TNF-α mRNA. In vivo, recombinant rat IL-1α and IL-1β enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1000 fold lower when IL-1 was injected centrally than when it was administered peripherally, indicating that they are centrally mediated. The relative potencies of recombinant rat IL-1α and IL-1β were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be involved in the various effects of IL-1 on the brain.