Reduced catecholamine response of lymphocytes from patients with rheumatoid arthritis

Catecholamines modulate lymphocyte function via stimulation of beta 2-adrenergic receptors (beta 2R). Previous investigations revealed a decreased density of beta 2R on peripheral blood mononuclear cells (PBMC) in patients with chronic rheumatic diseases. Aim of the present study Was to determine the impact of this decrease on catecholamine response of PBMC from patients with rheumatoid arthritis (RA) in vitro. PBMC from 17 patients with RA and 12 healthy blood donors (HD) were investigated. beta 2R were determined by a radioligand binding assay. The effects of epinephrine (E) and norepinephrine (NE) on PBMC proliferation were studied using cells activated With pokeweed mitogen (PWM) and monoclonal anti-CD3-antibodies (OKT3), respectively. In parallel, alpha(1)- or beta-receptor antagonist were added to the culture to determine the specificity of the catecholaminergic effects, results showed that depending on the stimulus and the catecholamine concentration employed E and NE exert inhibitory (OKT3) or stimulatory signals (PWM) on lymphocyte proliferation. Inhibitory effects could be abolished by adding beta-antagonist, while stimulatory signals were diminished after addition of alpha(1)- of beta-antagonist. Patients with RA showed a significantly reduced density of beta 2R compared to HD paralleled by a significantly reduced influence of catecholamines on lymphocyte function. The study demonstrates the intricate relationship between PBMC reactivity and catecholamine effects that are mediated via alpha(1)- and beta-adrenergic receptors. In this respect the reduced catecholamine response of PBMC from RA. patients may contribute to the pathogenic process of RA.