Hidroksizin Hidroklorürün Memeli Makrofajları Üzerindeki Etkilerinin İncelenmesi

Yıl 2022, , 652 - 658, 28.12.2022

Harika Topal Önal

https://doi.org/10.31832/smj.1082230

Öz

Amaç: Hidroksizin hidroklorür son yıllarda anksiyete bozukluğu, ruhsal sıkıntı ve gerginliğin tedavisinde yaygın olarak tercih edilen antihistaminik türevli bir ilaçtır. Literatürde Hidroksizin hidroklorürün bağışıklık sistemi üzerine etkileri ile ilgili yeterli çalışma mevcut değildir.
Gereç ve Yöntemler: Çalışmamızda J774.2 makrofaj hücre hattında lipopolisakkarit (LPS) tehlike sinyali varlığında ve yokluğunda 1, 5,10 ve 20 µg/ml hidroksizin hidroklorür uygulayarak proinflamatuvar sitokin seviyelerine etkilerini araştırdık. İstatistiksel analiz için Student t testi uygulandı (p<0.0001, N=3.) Tüm deney koşulları üçlü olarak test edildi.
Bulgular: Hidroksizin hidroklorür makrofaj hücrelerinde 24 saatlik inkübasyondan sonra tümör nekroz alfa (TNFα), interlökin 6 (IL-6), interlökin-12 subunit beta (IL12p40) ve granülosit makrofaj koloni uyarıcı faktör (GM-CSF) sitokin seviyelerini etkilemeyerek bağışıklık hücrelerini aktive etmedi. İmminostimülatör etki göstermeyen bu değerlerde istatistiksel olarak bir fark gözlenmedi.
Sonuç: Hidroksizin hidroklorür makrofaj hücreleri için imminostimülatör etki göstermediği için klinikte güvenli bir şekilde kullanılabilinir.

Anahtar Kelimeler

J774.2, Makrofaj, Sitokin, Hidroksizin Hidroklorür

Kaynakça

• 1. https://www.businesswire.com/news/home/20210426005303/en/Global-Antidepressants-Market-Report-2021-COVID-19-Causes-a-Surge-in-Demand-for-Antidepressant-Drugs-as-Mental-Health-Problems-Rise---ResearchAndMarkets.com
• 2. Oppong, E., Cato, A. C. (2015). Effects of glucocorticoids in the immune system. Glucocorticoid signaling 2015; 217-233
• 3. Cubała, W. J., Landowski, J., Dziadziuszko, M., Chrzanowska, A., Wielgomas, B. Magnesium, C-reactive protein, and cortisol in drug-naïve patients with short illness-duration, first episode major depressive disorder: possible immunomodulatory role for magnesium. Magnesium Research 2016; 24: 169-174
• 4. Demir, S., Atli, A., Bulut, M., İbiloğlu, A. O., Güneş, M., Kaya, M. C., Sır, A. Neutrophil–lymphocyte ratio in patients with major depressive disorder undergoing no pharmacological therapy. Neuropsychiatric disease and treatment 2015; 11: 2253
• 5. Wei J, Zhang M, Zhou J. Myeloid-derived suppressor cells in major depression patients suppress T-cell responses through the production of reactive oxygen species. Psychiatry Res 2015; 228:695–701
• 6. Hannestad J, Dellagioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 2011; 36:2452–2459
• 7. Dahl, J., Ormstad, H., Aass, H. C. D., Malt, U. F., Bendz, L. T., Sandvik, L., Andreassen, O. A. The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery. Psychoneuroendocrinology 2014; 45:77-86
• 8. Strawbridge, R., Arnone, D., Danese, A., Papadopoulos, A., Vives, A. H., Cleare, A. J. Inflammation and clinical response to treatment in depression: a meta-analysis. European Neuropsychopharmacology 2015;25:1532-1543
• 9. Brunoni, A. R., Machado-Vieira, R., Sampaio-Junior, B., Vieira, E. L., Valiengo, L., Benseñor, I. M., Teixeira, A. L. Plasma levels of soluble TNF receptors 1 and 2 after tDCS and sertraline treatment in major depression: results from the SELECT-TDCS trial. Journal of affective disorders 2015;185:209-213
• 10. Szałach, Ł. P., Lisowska, K. A., Cubała, W. J. The influence of antidepressants on the immune system. Archivum immunologiae et therapiae experimentalis 2019; 67:143-151
• 11. Lagier, B., Lebel, B., Bousquet, J., Pene, J. Different modulation by histamine of IL‐4 and interferon‐gamma (IFN‐γ) release according to the phenotype of human Th0, Th1 and Th2 clones. Clinical & Experimental Immunology 1997;108:545-551
• 12. Vannier E, Miller LC, Dinarella CA. Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors. J Exp Med 1991; 174:281-284
• 13. Van der Pouw Kraan, T. C., Snijders, A., Boeije, L. C., de Groot, E. R., Alewijnse, A. E., Leurs, R., Aarden, L. A. Histamine inhibits the production of interleukin-12 through interaction with H2 receptors. The Journal of clinical investigation 1998; 102:1866-1873
• 14. Elenkov, I. J., Webster, E., Papanicolaou, D. A., Fleisher, T. A., Chrousos, G. P., Wilder, R. L. Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors. The Journal of Immunology 1998:161(5):2586-2593
• 15. Parameswaran, N., and S. Patial. Tumor necrosis factor-α signaling in macrophages. Critical Reviews in Eukaryotic Gene Expression 2010; 20: 87–103
• 16. López-Abente, G., Mispireta, S.,Pollán, M. Breast and prostate cancer: an analysis of common epidemiological features in mortality trends in Spain. BMC cancer 2014;14(1): 1-10
• 17. Ince, M., A. Hausmann, M.V. Martínez-Díaz, D.M. Guldi, and T. Torres. Non-covalent versus covalent donor-acceptor systems based on near-infrared absorbing azulenocyanines and C60 fullerene derivatives. Chemical Communications 2012; 48:4058–4060
• 18. Ayaz F. Ruthenium pyridyl thiocyanate complex increased the production of pro-inflammatory TNFα and IL1β cytokines by the LPS stimulated mammalian macrophages in vitro. Molecular biology reports 2018; 45(6):2307-2312
• 19. Ayaz F., Yuzer A.. Immunostimulatory effect of Zinc Phthalocyanine derivatives on macrophages based on the pro-inflammatory TNFα and IL1β cytokine production levels M. Ince. Toxicol. In Vitro 2018; 53: 172–177
• 20. Önal, H. T., Yuzer, A., Ince, M., Ayaz, F. Photo induced anti-inflammatory activities of a Thiophene substituted subphthalocyanine derivative. Photodiagnosis and Photodynamic Therapy 2020; 30:101701
• 21. Gasparini, C., B.M. Foxwell, and M. Feldmann. RelB/p50 regulates TNF production in LPS-stimulated dendritic cells and macrophages. Cytokine 2013;61: 736–740
• 22. Jacobsen, P. L., Thorley, E. M., Curran, C. Real-world patient experience with sexual dysfunction and antidepressant use in patients with self-reported depression: A cross-sectional survey study. Neurology, Psychiatry and Brain Research 2020; 36:57-64
• 23. Landmann, R., Schaub, B., Link, S., Wacker, H.R. Unaltered monocyte function in patients with major depression before and after three months of antidepressive therapy. Biol. Psychiatry 1997;41: 675–681
• 24. Lee, K.M., Kim, Y.K. The role of IL-12 and TGF-beta1 in the pathophysiology of major depressive disorder. Int. Immunopharmacol 2006; 6:1298–1304
• 25. Müller, N., Hofschuster, E., Ackenheil, M., Mempel, W., & Eckstein, R. (1993). Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 1993; 17: 713-730
• 26. Haapakoski, R., Mathieu, J., Ebmeier, K. P., Alenius, H., & Kivimäki, M. (2015). Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder. Brain, behavior, and immunity 2015; 49: 206-215
• 27. Dowlati Y, Herrmann N, Swardfager W et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010; 67: 446-457
• 28. Hannestad J, Dellagioia N, Bloch M. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 2011; 36: 2452-2459
• 29. Kubera, M., Curzytek, K., Majewska-Szczepanik, M., Szczepanik, M., Marcinska, K., Ptak, W., Leskiewicz, M., Maes, M., Basta-Kaim, A., Budziszewska, B., Detka, J.,Duda, W., Lason, W. Inhibitory effect of antidepressant drugs on contact hypersensitivity reaction. Pharmacol. Rep 2012; 64:714–722
• 30. Curzytek, K., Kubera, M., Szczepanik, M., Basta-Kaim, A., Leskiewicz, M., Budziszewska, B., Lason, W., Maes, M. Crosstalk between contact hypersensitivity reaction and antidepressant drugs. Pharmacol. Rep 2013; 65: 1673–1680
• 31. Lin, A., Song, C., Kenis, G., Bosmans, E., De Jongh, R., Scharpe, S., Maes, M. The in vitro immunosuppressive effects of moclobemide in healthy volunteers. J. Affect. Disord 2000; 58: 69–74
• 32. Xia, Z., DePierre, J.W., Nassberger, L. Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology 1996; 34: 27–37