Experimental Physiology Exp Physiol 98.3 (2013) pp 665–678 665 Research Paper Research Paper Adrenal hormone deprivation affects macrophage catecholamine metabolism and β 2 -adrenoceptor density, but not propranolol stimulation of tumour necrosis factor-α production Stanislava Stanojevi´ c 1 , Mirjana Dimitrijevi´ c 1 , Nataˇ sa Kuˇ strimovi´ c 1 , Katarina Miti´ c 1 , Vesna Vuji´ c 2 and Gordana Leposavi´ c 3 1 Immunology Research Centre ‘Branislav Jankovi´ c’, Institute of Virology, Vaccines and Sera ‘Torlak’, Belgrade, Serbia 2 Department of Chemistry, Faculty of Medicine, University of Belgrade, Belgrade, Serbia 3 Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia New Findings  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-α production in rat macrophages by altering the autocrine/paracrine action of catecholamines.  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 β 2 -adrenoceptor expression (due to lack of adrenal catecholamines). However, notwithstanding these changes, propranolol treatment increased lipopolysaccharide-stimulated tumour necrosis factor-α 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 β 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-α (TNF-α) 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-α production in vitro and for expression of β 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 β 2 -adrenoceptor blockade, increased production of TNF-α by macrophages in both non- operated and adrenalectomized rats (showing dramatically enhanced TNF-α production due to a lack of circulating glucocorticoids) for the same value. The expression of β 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 β 2 -adrenoceptor expression in adrenalectomized rats. C  2013 The Authors. Experimental Physiology C  2013 The Physiological Society DOI: 10.1113/expphysiol.2012.070524 ) at Università Insubria on September 16, 2013 ep.physoc.org Downloaded from Exp Physiol (