Enhancement or loss of the hypophagic effect of interleukin-1 upon chronic administration

To further characterize the effect of interleukin-1 on food intake, we tested whether a tolerance to the hypophagic effect of recombinant human interleukin-1 beta (rhIL-1 beta) develops with repeated injections or continuous infusion in rats. Daily intraperitoneal (IP) injections of rhIL-1 beta (25,000 LAF units/kg b.wt.) for 4 days did not result in tolerance to rhIL-1 beta's hypophagic effect. The hypophagic effect of the same dose of rhIL-1 beta actually increased if injections were given every second day, when the hypophagic effect of the preceding injection had subsided. A dose of rhIL-1 beta that usually did not affect food intake (5000 LAF units/kg b.wt.) reduced food intake if injected repeatedly. Continuous infusion of rhIL-1 beta (25,000 LAF units/kg b.wt/day) via IP-implanted osmotic minipumps caused a strong initial suppression of feeding followed by the development of tolerance to the hypophagic effect of the infused rhIL-1 beta. Nevertheless, hypophagia caused by a subsequent IP injection of rhIL-1 beta (25,000 LAF units/kg b.wt.) was enhanced. As specific antibodies to rhIL-1 beta could be detected in sera of only three of 11 rhIL-1 beta-infused rats, the observed tolerance was probably not due to a humoral immune response. The results demonstrate that, dependent on test conditions, chronic administration of rhIL-1 beta in the rat can lead to an enhancement or to a loss of its hypophagic effect. The reasons for this difference remain unclear.