Beta 2-Adrenergic Receptor Functionality And Genotype In Two Different Models Of Chronic Inflammatory Disease: Liver Cirrhosis And Osteoarthritis

The present study was designed to investigate the functional status of 2 adrenoceptors (2AR) in two models of chronic inflammatory disease: Liver cirrhosis (LC) and osteoarthritis (OA). The 2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte 2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13 +/- 4 mmHg, CHILD 7 +/- 2 and MELD 11 +/- 4 scores), OA patients (n=30, 84% Kellgren-Lawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 10(-9) to 10(-4) mM), and 2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. 2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the 2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the 2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes.