Nociceptin (N/OFQ) And Immune Modulation

Opioids are reported to modulate the functioning of the immune system through central and peripheral mechanisms, including direct interactions with opioid receptors on peripheral immune cells. Opioid receptors can be classified as classical (naloxone-sensitive); MOP (mu), KOP (kappa), DOP (delta) and non-classical (naloxone-insensitive); NOP (nociceptin/orphanin FQ as an endogenous ligand) receptors. In this thesis, it is shown that classical (MOP, KOP and DOP) opioid receptor mRNA (and hence the receptor protein) is not expressed in peripheral whole human blood, whereas a consistent expression of (non-classical) NOP receptor mRNA is observed which also showed decreased NOP mRNA expression in response to in vitro sepsis. The effects of NOP stimulation on cell migration (polymorphonuclear [PMN] and eosinophil-like cells [EOL-1]) and the release of inflammatory mediators in vitro were also investigated revealing concentration dependent inhibition of cell migration associated with NOP stimulation. The effect of NOP stimulation on cytokine balance was difficult to detect because of the small number of cells examined and a significant dilution effect. Certain acute inflammatory conditions and disease processes change the balance between circulating neutrophils and lymphocytes. A high neutrophil to lymphocyte ratio (NLR) indicates a relatively higher number of circulating neutrophils accompanied by an imbalance of inflammatory mediators. The link between NLR and inflammatory cytokine in vivo was also investigated in this thesis but was proven to be inconclusive in view of the small sample size; however, it may warrant further investigation in the future. These results indicate that the N/OFQ-NOP receptors—but not the classical opioid system—are involved in modulating peripheral immune cell function that may be a future therapeutic target.