PF upregulates circulation of multiple immunomodulatory metabolites
TNF-α, Tumor necrosis
TUMOR NECROSIS
To determine the potential plasma-borne mediators of the observed anti-inflammatory effects of PF, we analyzed the dataset of significantly upregulated metabolites between the fasted and baseline states to find metabolites that had previously been shown to have effects on immune cell functionality. Although BHB was highly upregulated during PF (Metabolites upregulated during fasting induce anti-inflammatory effects in macrophage. Tumor necrosis factor alpha (TNF-α) secretion from citrullinated fibrinogen immune complex (cFb IC)-stimulated primary human macrophage treated with beta-hydroxybutyrate (BHB), spermidine, 1-methylnicotinamide (1-MNA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) at a final concentration of 1–10 nM (A). The TNF-α levels from unstimulated macrophage are shown as negative control values, and the TNF-α levels from stimulated macrophage without any other treatment are shown as positive control values. TNF-α secretion from cFb IC-stimulated primary human macrophage treated with spermidine (100 μM), 1-MNA (100 μM), PEA (10 μM), OEA (10 μM), and a combination treatment (combo) of all 4 metabolites at their individual concentrations (B). These concentrations were used for all vitro analyses (B–F). The negative and positive control values for all in vitro metabolite analyses (B–F) were generated from unstimulated macrophage or stimulated macrophage with no other treatment, respectively, as described earlier. Significance between treatments and controls for all in vitro analyses (B–F) is denoted by their assigned letter (a–f) where groups that share an assigned letter in common were found to have no significant differences (