Macrophages play a crucial role in coordinating the immune response and regulating inflammatory balance. They exist as two main phenotypes: M1 macrophages, which are pro-inflammatory and secrete cytokines like TNF to amplify the immune response, and M2, which are anti-inflammatory and promote tissue healing by secreting cytokines like IL-10. The balance between these phenotypes is essential for effective infection control, and disruptions can lead to autoimmune diseases, severe infections, and other inflammatory disorders. Understanding the modulation of these phenotypes is key for developing effective therapies.
This project investigates the interactions between the sympathetic nervous system (SNS) and the immune system by treating a monocyte-like cell line with β-adrenergic receptor (β-AR) agonist and antagonist drugs. While previous studies showed that β2-AR drugs have anti-inflammatory properties in macrophages (Kast, 2000; Szelenyi et al., 2000), research on their effects on M1/M2 macrophage phenotypes and receptor selectivity is limited. This project aims to address these gaps to better understand the interplay between the SNS and immune system.
β1- and β2-AR expression was confirmed in both macrophage phenotypes, with ADRB1 and ADRB2 genes upregulated in M1-like cells (with IFNγ) and downregulated in M2-like cells. Isoproterenol, a non-selective β-AR agonist, decreased TNF in M1-like cells and increased IL-10 in M2-like cells. These effects were reversed by the non-selective β-AR antagonist bupranolol but not by the β2-selective antagonist ICI 118,551. Terbutaline, a β2-selective agonist, showed similar trends and was reversed by both antagonists. This research demonstrates that SNS activity influences immune responses, promoting an anti-inflammatory profile through β-AR activation. These findings suggest potential therapeutic strategies using β-AR drugs for inflammatory and autoimmune conditions.