Effect of orphanin FQ on interleukin-1beta mRNA transcripts in the rat CNS.

To elucidate the mechanism of orphanin FQ on neuroimmune modulation, the relationship between orphanin FQ and interleukin-1beta in the rat CNS in vivo and in vitro was investigated. In our experiments, it was found that orphanin FQ and interleukin-1beta mRNA transcripts showed a similar distribution in cerebral cortex, hippocampus and hypothalamus. By using the in situ hybridization technique, down-regulation of interleukin-1beta mRNA transcripts by central administration of orphanin FQ was further identified in the traumatic animal model. Similar inhibitory effects were also observed on the number of microglia in the CNS. The effects produced by orphanin FQ were abolished by combination with its receptor (OP(4))-specific antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2), which suggested that the function of orphanin FQ might be attributable to the OP(4) pathway. However, the effect on the number of astrocytes in the CNS remained unchanged, despite evidence that OP(4) is expressed on astrocytes as well as on neurons and microglia. When analyzed by reverse transcription-polymerase chain reaction, interleukin-1beta gene expression was observed to be enhanced and inhibited in primary neuron and microglial cell cultures exposed to orphanin FQ respectively. Interleukin-1beta gene expression in astrocyte cultures was not affected by treatment with orphanin FQ. Our findings suggest that the neuroimmune function of orphanin FQ might be dependent on interleukin-1beta derived from microglia, and the interaction between microglia and neurons.