The effect of nortriptyline and its combination with mometasone on secretion of IL-6 and IL-8 by stimulated blood mononuclear cells in vitro

Glucocorticosteroids (GCS) are often the medication of choice for chronic inflammation. Since not all patients are equally sensitive to GCS, certain efforts are undertaken to increase sensitivity and complement glucocorticosteroid therapy with other nonsteroidal medications that can enhance the anti-inflammatory effect of GCS. The tricyclic antidepressant nortriptyline has demonstrated anti-inflammatory properties in several experimental studies, as well as the ability to complement the action of GCS. The aim of this study was to investigate the effects of nortriptyline, as well as its combination with mometasone, on blood mononuclear cells (MNCs) under conditions of stimulated immune responses (IR) of types 1, 2, and 17. In isolated MNCs from six healthy donors, IR type I, type 2, or type 17 were stimulated in the presence of nortriptyline, mometasone, or their combination by adding recombinant activator proteins (IL-2, IL-25, IL-33, thymic stromal lymphopoietin (TSLP), IL-12, IL-1β, IL-23). After three days, the concentration of IL-6 and IL-8 was determined in the supernatants by enzyme-linked immunosorbent assay. In the presence of nortriptyline at a final concentration of 10-5 M, IR type 2 and type 17 were accompanied by a decrease in IL-6 concentration. Addition of a combination of mometasone and nortriptyline to the MNC culture medium under conditions of IR type II activation had a potentiating effect. This was evidenced by a decrease in IL-6 and IL-8 secretion compared to the use of mometasone alone. The study demonstrates the ability of nortriptyline to suppress the secretion of proinflammatory cytokines by blood cells, which is selective and dependent on the type of immune response.