Background: Peptide-YY is synthesised and secreted by specialised cells in the ileum and colon. Levels increase following food intake, having a satiety effect. Baseline and postprandial levels of PYY were found to be lower in obese subjects compared to lean, negatively correlating with the subjects BMI, however obese subjects were sensitive to the anorectic effects of PYY when given exogenous PYY.
Hypothesis: We have recently demonstrated that another prandial gastrointestinal hormone, glucagon-like peptide 1 (GLP 1), is immunomodulatory and has therapeutic effects in inflammatory disease. We proposed that PYY would play a role in regulating human natural killer (NK) and invariant natural killer T (iNKT) cells.
Methods: We looked for the presence of a functional PYY on iNKT cells and the downstream transcription factors. We investigated the in vitro effects of PYY and a long acting PYY analogue Y-59 treatment on iNKT cell function (cytokine production and tumour cell lysis). Finally we examined the direct anti-tumour activity of Y-59 treatment (tumour cell growth and colony formation).
Results: Activation with PYY and its analogue Y-59 resulted in modest modulation of iNKT cell cytokine production with inhibition of IFN-γ (P<0.05) secretion but not IL4 (P=0.7). Both PYY and Y-59 significantly increased iNKT cell and NK cell cytolytic degranulation in vitro. The long acting PYY analogue Y-59 reduced tumour cell growth (P<0.01).
Conclusion/interpretation: PYY displays immunomodulatory/anti-tumour effects via its actions on human iNKT and NK cells and direct effects on tumour cell growth. This suggests that the gastrointestinal hormone system produces immunomodulatory peptides, which may be targeted in obesity related diseases such as cancer.