SUPPRESSION OF PRO-INFLAMMATORY PRODUCTS CYTOKINES IN NATURAL KILLERS OF PATIENTS' BLOOD WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE UNDER THE INFLUENCE OF NORTRIPTYLINE

Aim. To determine the ability of nortriptyline, alone and in combination with budesonide, to inhibit the production of pro-inflammatory cytokines in the peripheral blood natural killer (NK) cells of patients with chronic obstructive pulmonary disease (COPD) and to establish the molecular mechanisms of the combined action of these drugs. Material and methods. Blood cells from COPD patients (n=21) were incubated with budesonide, nortriptyline, or their combination. Cytokine production, expression of glucocorticoid receptor β (GRβ), histone deacetylase 2 (HDAC2), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) in NK cells were analyzed by flow cytometry. Results. The combination of nortriptyline (10 μM) and budesonide (10 nM) reduced the synthesis of interleukin 4 (IL-4), IL-8, interferon γ, tumor necrosis factor α as well as the expression of GRβ and p-p38 MAPK in NK cells; it also increased the expression of HDAC2 more significantly than budesonide alone. Conclusions. Nortriptyline enhances the anti-inflammatory effect of budesonide by altering the expression of HDAC2, GRβ, p-p38 MAPK in peripheral blood NK cells of patients with COPD. The data obtained indicate the advisability of combining nortriptyline with budesonide for the treatment of COPD.