Weingarten S, Savoldelli D, Langhans W
Institute for Animal Sciences, Swiss Federal Institute of Technology, Zurich.
Physiol Behav. 1992 Nov;52(5):831-7. doi: 10.1016/0031-9384(92)90358-9.
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.
为了进一步明确白细胞介素-1对食物摄入的影响，我们测试了大鼠反复注射或持续输注重组人白细胞介素-1β（rhIL-1β）后是否会对其食欲减退作用产生耐受性。每天腹腔注射rhIL-1β（25,000 LAF单位/千克体重），连续4天，并未导致对rhIL-1β食欲减退作用产生耐受性。如果每隔一天注射一次，在前一次注射的食欲减退作用消退时，相同剂量的rhIL-1β的食欲减退作用实际上会增强。通常不影响食物摄入的rhIL-1β剂量（5000 LAF单位/千克体重）反复注射时会减少食物摄入。通过腹腔植入的渗透微型泵持续输注rhIL-1β（25,000 LAF单位/千克体重/天）会导致最初强烈抑制进食，随后对输注的rhIL-1β的食欲减退作用产生耐受性。然而，随后腹腔注射rhIL-1β（25,000 LAF单位/千克体重）引起的食欲减退会增强。由于在11只输注rhIL-1β的大鼠中只有3只的血清中能检测到针对rhIL-1β的特异性抗体，因此观察到的耐受性可能不是由于体液免疫反应。结果表明，取决于测试条件，大鼠长期给予rhIL-1β可导致其食欲减退作用增强或丧失。这种差异的原因尚不清楚。
