Catecholamines promote an M2 macrophage activation phenotype (P1299)

Abstract

Abstract Based on their function, activated macrophages are categorized as having M1 or M2 phenotypes. M1 macrophages are pro-inflammatory and mediate host defenses against pathogens. M2 macrophages promote immunosuppression and wound healing. Here, we report significant alterations in activated macrophage phenotypes by catecholamines. Epinephrine and norepinephrine dramatically reduced TNF production by LPS-stimulated mouse macrophages in vitro, with IC50s of 5.5 and 700 nM, respectively. Co-treatment of macrophages with LPS and either catecholamine promoted an anti-inflammatory phenotype, including increased IL-10 mRNA and protein production. Interestingly, in LPS-stimulated macrophages, co-presence of either catecholamine reduced iNOS (a marker for M1 macrophages) mRNA by 75-81%, while Arginase (M2 marker) mRNA expression was enhanced by 8.3 to 13.5-fold. Therefore, catecholamines promoted an M2-like macrophage activation phenotype. This effect was determined to be mediated through the beta-2 adrenergic receptor and the phosphoinositol 3-kinase pathway. Catecholamines modulated both MyD88-dependent and MyD88-independent signaling through several different TLRs. In rodent models of acute lung injury, co-administration of a beta-2 adrenergic receptor agonist reduced inflammatory mediator production and prevented injury. These data have significant clinical implications for diseases ranging from allergy and asthma to sepsis.