Adrenal hormone deprivation affects macrophage catecholamine metabolism and 2-adrenoceptor density, but not propranolol stimulation of tumour necrosis factor- production

Abstract

New Findings center dot What is the central question of this study? Glucocorticoids modulate extraglandular catecholamine metabolism and adrenoceptor expression in many cell types. Catecholamines modulate the production of inflammatory mediators by macrophages. It was hypothesized that adrenal hormones affect tumour necrosis factor- production in rat macrophages by altering the autocrine/paracrine action of catecholamines. center dot What is the main finding and its importance? In rat macrophages, adrenalectomy increased tyrosine hydroxylase expression, decreased monoamine oxidase-A mRNA expression (due to the absence of adrenal catecholamines and glucocorticoids, respectively) and augmented 2-adrenoceptor expression (due to lack of adrenal catecholamines). However, notwithstanding these changes, propranolol treatment increased lipopolysaccharide-stimulated tumour necrosis factor- production in macrophages from adrenalectomized and non-operated rats to a similar extent. Catecholamines modulate the production of inflammatory mediators by macrophages in an autocrine/paracrine manner. They also tune 2-adrenoceptor expression. Glucocorticoids influence catecholamine metabolism and adrenoceptor expression in many cell types. We hypothesized that adrenal hormones affect the production of tumour necrosis factor- (TNF-) and NO by macrophages by altering the modulatory influence of catecholamines. To prove the hypothesis, peritoneal exudate macrophages from propranolol-treated non-operated and adrenalectomized rats and from corticosterone-supplemented adrenalectomized rats were examined for lipopolysaccharide-stimulated NO and TNF- production in vitro and for expression of 2-adrenoceptors and major catecholamine-metabolizing enzymes. Glucocorticoid deprivation increased NO production by macrophages, whereas 4 days of propranolol treatment was ineffective in this respect. However, propranolol treatment, via 2-adrenoceptor blockade, increased production of TNF- by macrophages in both non-operated and adrenalectomized rats (showing dramatically enhanced TNF- production due to a lack of circulating glucocorticoids) for the same value. The expression of 2-adrenoceptor was increased in peritoneal macrophages that were freshly isolated from non-operated, propranolol-treated and adrenalectomized rats (due to adrenal catecholamine deficiency). Propranolol did not affect macrophage 2-adrenoceptor expression in adrenalectomized rats. Given that propranolol increased the density of macrophage tyrosine hydroxylase expression only in non-operated rats and affected the mRNA expression of monoamine oxidase-A in neither non-operated nor adrenalectomized animals, a significant influence of propranolol on peritoneal exudate cell noradrenaline content was found only in non-operated rats. A lack of circulating adrenal hormones also affected noradrenaline metabolism and content in peritoneal exudate cells including macrophages. Collectively, despite differences in the abundance of macrophage catecholamine2-adrenoceptor system components and in the TNF- response to lipopolysaccharide between adrenalectomized and non-operated rats, propranolol increased TNF- production by the same amount in macrophages from these two groups of animals.