BIOLOGICAL-ACTIVITY AND BRAIN ACTIONS OF RECOMBINANT RAT INTERLEUKIN-1-ALPHA AND INTERLEUKIN-1-BETA

IL-1 alpha and IL-1 beta have potent effects on the central nervous sy stem resulting in fever, activation of the hypothalamic-pituitary-adre nal axis and behavioural depression. These effects have mainly been st udied in rats, using recombinant human and mouse IL-1, Because IL-1 al pha and IL-1 beta show some species specificity in the potency of thei r biological activities, the objective of the present work was to dire ctly compare the effects of recombinant rat IL-1 alpha and IL-1 beta i n the rat system as a first step to dissect out the mechanisms that ar e involved in these effects. In vitro, recombinant rat IL-1 alpha and IL-1 beta bound with the same affinity as human IL-1 to the rat insuli noma Rin m5F cell line that mainly expresses type I IL-1 receptors, Th is binding activated IL-l receptors, as shown by induction of the synt hesis of TNF-a mRNA, In vivo, recombinant rat IL-1 alpha and IL-1 beta enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtai ned at doses 100-1,000 fold lower when IL-1 was injected centrally tha n when it was administered peripherally, indicating that they are cent rally mediated. The relative potencies of recombinant rat IL-1 alpha a nd IL-1 beta were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be i nvolved in the various effects of IL-1 on the brain.