Nociceptin system as a target in sepsis?

Róisín Thomas,David G Lambert,Jonathan P Thompson,Cordula Stover

doi:10.1007/s00540-014-1818-6

Róisín Thomas, David G Lambert + Show 2 more

Open Access

https://doi.org/10.1007/s00540-014-1818-6

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Abstract

The nociceptin system comprises the nociceptin receptor (NOP) and the ligand nociceptin/orphanin FQ (N/OFQ) that binds to the receptor. The archetypal role of the system is in pain processing but the NOP receptor is also expressed on immune cells. Activation of the NOP receptor is known to modulate inflammatory responses, such as mast-cell degranulation, neutrophil rolling, vasodilation, increased vascular permeability, adhesion molecule regulation and leucocyte recruitment. As there is a loss of regulation of inflammatory responses during sepsis, the nociceptin system could be a target for therapies aimed at modulating sepsis. This review details the known effects of NOP activation on leucocytes and the vascular endothelium and discusses the most recent human and animal data on the role of the nociceptin system in sepsis.

Highlights

The inflammatory response involves activation of several cell types in blood and tissues to initiate a cascade of events to remove pathogens and repair damaged tissue
We found that nociceptin/orphanin FQ (N/OFQ)-induced macromolecular leak could be inhibited by H1 and H2 receptor antagonists or by UFP-101.18 UFP-101 is a peptide antagonis that is selective for the nociceptin receptor (NOP) receptor
19 We found that N/OFQ elicited other inflammatory responses such as vasodilation and increased rolling and adhesion of leucocytes on the endothelium[18]

Summary

Introduction

The inflammatory response involves activation of several cell types in blood and tissues to initiate a cascade of events to remove pathogens and repair damaged tissue. TNF-α, and IL-1β exposure causes N/OFQ mRNA concentrations to increase in rat astrocytes[41] and incubation of unstimulated rat splenocytes with IL-1β increases N/OFQ secretion.[11] The effects of TNF-α on neutrophils have been discussed previously but TNF-α has other pro-inflammatory actions such as upregulation of the expression of intracellular adhesion molecules that are important for leucocyte extravasation, such as ICAM-1 and VCAM-126 on endothelial cells.

Results

Conclusion