Immunomodulatory activity of orphanin FQ/nociceptin on traumatic rats.

Acta Pharmacol Sin

National Key Laboratory of Medical Neurobiology, Department of Neurobiology, Medical College of Fudan University, Shanghai 200032, China.

Published: April 2002

Aim: To explore the neuro-immune modulatory effect of orphanin FQ/nociceptin (OFQ) and opioid receptor like 1 (ORL1) receptor on the traumatic rats.

Methods: The quantitative method of immuno-cytochemistry and i n situ hybridization combined with cytokine bioassay were used to detect the expression of endogenous OFQ and ORL1 and the production of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) from peritoneal macrophage.

Results: Strong signals for both OFQ immuno-reactive cells and ORL1 mRNA were detected in cerebral cortex, hippocampus, and hypothalamus in normal condition, whereas they were significantly reduced after trauma (P<0.05). However, the production of IL-1 and TNF-alpha from peritoneal macrophage was increased, when expressed as percentage of enhancement, the increment attained to 233 % and 521 % (sample dilution 1:4), 195 % and 566 % (1:8), 233 % and 757 % ( 1:16), 214 % and 622 % (1:32), respectively, after trauma. After icv injection of OFQ at doses of 0.055 nmol, 0.55 nmol, and 2.75 nmol, the units of IL-1 and TNF-alpha were reversed (P<0.05); however, the action of OFQ (0.55 nmol) was blocked by ORL1 selective antagonist [phe1psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2.

Conclusion: OFQ and ORL1, the new opioid peptide system, are involved in the immune response elicited by traumatic stress.

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