The inhibitory effect of mometasone and nortriptyline on the production of proinflammatory cytokines by blood mononuclear cells of patients with allergic rhinitis under conditions of stimulated immune response
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa; it develops when the immune system reacts to an allergen. Side effects of topical glucocorticosteroids (GCS) used for AR treatment, the development of steroid resistance in patients and the continuing increase in morbidity explain the clear need to search for new approaches for AR treatment. The tricyclic antidepressant nortriptyline has demonstrated anti-inflammatory properties in a number of experimental studies, as well as its ability to complement the action of corticosteroids. The aim of this study was to compare the effects of nortriptyline and the synthetic GCS mometasone on the culture of mononuclear cells (MNC) of AR patients. Blood MNCs from six AR patients were cultured in the presence of nortriptyline or mometasone, and then type 1, type 2, or type 17 immune response (IR) were stimulated by adding recombinant activator proteins (IL-2, IL-25, IL-33, TSLP, IL-12, IL-1β, IL-23). After 3 days, concentrations of proinflammatory cytokines TNF-α, IFN-γ, IL-6, IL-8, and IL-4 were determined in cell supernatants by enzyme immunoassay. Mometasone (10⁻⁸ M final concentration) effectively suppressed the secretion of proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-8 under conditions of stimulation of IR of all types. A similar decrease in secretion, although less pronounced, occurred when stimulated cells were cultured in the presence of nortriptyline. The concentration of TNF-α in the culture medium decreased under these conditions both with stimulation of type 1, type 2, and type 17 IR. The level of IFN-γ secretion decreased only in the case of type 1 and type 17 IR as compared to MNCs with the stimulated IR, which were cultured without this inhibitor. The level of IL-6 secretion decreased only in the culture medium of cells with stimulated type 1 and type 2 IR and IL-8 secretion decreased only under conditions of stimulated type 1 IR. This study has shown that mometasone and nortriptyline are able to suppress the secretion of proinflammatory cytokines by blood cells; their effect is selective and depends on the IR type.
Mironova T.V., Tahanovich A.D., Kadushkin A.G., Makarevich V.V., Shilovskiy I.P., Khaitov M.R. (2025) The inhibitory effect of mometasone and nortriptyline on the production of proinflammatory cytokines by blood mononuclear cells of patients with allergic rhinitis under conditions of stimulated immune response. Biomeditsinskaya Khimiya, 71(4), 300-307.
Mironova T.V. et al. The inhibitory effect of mometasone and nortriptyline on the production of proinflammatory cytokines by blood mononuclear cells of patients with allergic rhinitis under conditions of stimulated immune response // Biomeditsinskaya Khimiya. - 2025. - V. 71. -N 4. - P. 300-307.
Mironova T.V. et al., "The inhibitory effect of mometasone and nortriptyline on the production of proinflammatory cytokines by blood mononuclear cells of patients with allergic rhinitis under conditions of stimulated immune response." Biomeditsinskaya Khimiya 71.4 (2025): 300-307.
Mironova, T. V., Tahanovich, A. D., Kadushkin, A. G., Makarevich, V. V., Shilovskiy, I. P., Khaitov, M. R. (2025). The inhibitory effect of mometasone and nortriptyline on the production of proinflammatory cytokines by blood mononuclear cells of patients with allergic rhinitis under conditions of stimulated immune response. Biomeditsinskaya Khimiya, 71(4), 300-307.
References
Li P., Tsang M.S.-M., Kan L.L.-Y., Hou T., Hon S.S.-M., Chan B.C.-L., Chu I.M.-T., Lam C.W.-K., Leung P.-C., Wong C.-K. (2022) The immuno-modulatory activities of pentaherbs formula on ovalbumin-induced allergic rhinitis mice via the activation of Th1 and Treg cells and inhibition of Th2 and Th17 cells. Molecules, 27(1), 239. CrossRef Scholar google search
Prosekova E.V., Dolgopolov M.S., Sabynych V.A. (2020) Gene polymorphism, spontaneous and induced production of interleukin 4 and interferon gamma by peripheral blood cells in children with asthma. Russian Medical Review, 4(1), 10–14. CrossRef Scholar google search
Yang T., Li Y., Lyu Z., Huang K., Corrigan C.J., Ying S., Wang W., Wang C. (2017) Characteristics of proinflammatory cytokines and chemokines in airways of asthmatics: relationships with disease severity and infiltration of inflammatory cells. Chin. Med. J., 130(17), 2033–2040. CrossRef Scholar google search
Arefieva N.A., Aznabaeva L.F. (2009) Immune reactions of the nasal mucosa: cytological diagnostics, treatment methods. Consilium Medicum, 11(11), 30–33. Scholar google search
Yang G., Suo L.-M., Geng X.-R., Zeng X.-H., Liu J.-Q., Liu Z.-Q., Li M., Chen Y.-R., Hong J.-Y., Xue J.-M., Yang P.-C. (2022) An eosinophil-Sos1-RAS axis licenses corticosteroid resistance in patients with allergic rhinitis. Immunobiology, 227(3), 152215. CrossRef Scholar google search
Ohta N., Noguchi N., Takahashi T., Suzuki T., Kakuta R., Suzuki Y., Awataguchi T., Suzuki T., Takahashi Y., Shoji F., Wada K., Kawano T., Ono I., Kusano Y., Miyasaka T., Osafune H., Matsutani S., Yaginuma Y., Ishida Y., Saito Y., Yamazaki M., Ikeda R. (2018) The expression of 11 beta hydroxysteroid dehydrogenase in severe allergic rhinitis. Otolaryngol. Pol., 73(2), 18–22. CrossRef Scholar google search
Han M., Lee D., Lee S.H., Kim T.H. (2021) Oxidative stress and antioxidant pathway in allergic rhinitis. Antioxidants, 10(8), 1266. CrossRef Scholar google search
Howes S., Hartmann-Boyce J., Livingstone-Banks J., Hong B., Lindson N. (2020) Antidepressants for smoking cessation. Cochrane Database Syst. Rev., 4(4), CD000031. CrossRef Scholar google search
Gillman P.K. (2007) Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br. J. Pharmacol., 151(6), 737–748. CrossRef Scholar google search
Kadushkin A., Tahanovich A., Movchan L., Levandovskaya O., Shman T. (2021) Nortriptyline enhances corticosteroid sensitivity of blood T cells from patients with chronic obstructive pulmonary disease. J. Physiol. Pharmacol., 72(5), 793–805. CrossRef Scholar google search
Mercado N., To Y., Ito K., Barnes P.J. (2011) Nortriptyline reverses corticosteroid insensitivity by inhibition of phosphoinositide-3-kinase-δ. J. Pharmacol. Exp. Ther., 337(2), 465–470. CrossRef Scholar google search
Lehár J., Krueger A.S., Avery W., Heilbut A.M., Johansen L.M., Price E.R., Rickles R.J., Short G.F. 3rd, Staunton J.E., Jin X., Lee M.S., Zimmermann G.R., Borisy A.A. (2009) Synergistic drug combinations tend to improve therapeutically relevant selectivity. Nat. Biotechnol., 27(7), 659–666. CrossRef Scholar google search
Kadushkin A.G., Tahanovich A.D., Movchan L.V., Dziadzichkina V.V., Levandovskaya O.V., Shman T.V. (2022) Nortriptyline overcomes corticosteroid resistance in NK and NKT-like cells from peripheral blood of patients with chronic obstructive pulmonary disease. Research Results in Pharmacology, 8(1), 59–70. CrossRef Scholar google search
Kadushkin A.G., Tahanovich A.D., Khodosovskaya E.V., Kolesnikova T.S. (2023) Suppression of pro-inflammatory cytokine production in peripheral blood natural killer cells of patients with chronic obstructive pulmonary disease by nortriptyline. Journal of Grodno State Medical University, 21(1), 32–39. CrossRef Scholar google search
Hochhaus G. (2008) Pharmacokinetic/pharmacodynamic profile of mometasone furoate nasal spray: potential effects on clinical safety and efficacy. Clin Ther., 30(1), 1–13. CrossRef Scholar google search
Mullol J., de Borja Callejas F., Martínez-Antón M.A., Méndez-Arancibia E., Alobid I., Pujols L., Valero A., Picado C., Roca-Ferrer J. (2011) Mometasone and desloratadine additive effect on eosinophil survival and cytokine secretion from epithelial cells. Respir. Res., 12(1), 23. CrossRef Scholar google search
Schiffer M., Peters K., Peters M. (2022) Comparison of airway remodeling in two different endotypes of allergic asthma. Int. Arch. Allergy. Immunol., 83(7), 714–725. CrossRef Scholar google search
Simbirtsev A.S. (2021) Cytokines and their role in immune pathogenesis of allergy. Russian Medical Inquiry, 5(1), 32–37. CrossRef Scholar google search
Arebro J., Ekstedt S., Hjalmarsson E., Winqvist O., Kumlien Georén S., Cardell L.-O. (2017) A possible role for neutrophils in allergic rhinitis revealed after cellular subclassification. Sci. Rep., 7, 43568. CrossRef Scholar google search
Lavinskiene S., Jeroch J., Malakauskas K., Bajoriuniene I., Jackute J., Sakalauskas R. (2012) Peripheral blood neutrophil activity during Dermatophagoides pteronyssinus-induced late-phase airway inflammation in patients with allergic rhinitis and asthma. Inflammation, 35(4), 1600–1609. CrossRef Scholar google search
Mironova T.V., Taganovich A.D., Kadushkin A.G., Makarevich V.V., Shilovsky I.P., Khaitov M.R. (2024) The role of immune response components of the first and seventeenth types in the development of allergic diseases of the respiratory system. Vestnik Moskovskogo Universiteta. Seriya 16. Biologiya, 79(4), 280–286. CrossRef Scholar google search
Zhang N., van Crombruggen K., Holtappels G., Lan F., Katotomichelakis M., Zhang L., Högger P., Bachert C. (2014) Suppression of cytokine release by fluticasone furoate vs. mometasone furoate in human nasal tissue ex-vivo. PLOS One, 9(4), e93754. CrossRef Scholar google search
