Histamine H4 receptor is a potential target for COVID-19 treatment
Keywords:
COVID-19, Histamine, H4R, Histamine H4 receptorAbstract
Pulmonary fibrosis and cytokine storms are two major complications in COVID-19 patients that can decrease life quality after recovery and even cause death. Histamine H4 Receptor (H4R) antagonists prevent lung fibrosis and reduce TNF-α and IL-6 secretion in several immune-mediated diseases. T-helper cell 17 (TH17), which is an important inflammatory effector in COVID-19 pathogenesis, expresses H4Rs on its surface. The stimulation of these receptors results in IL-17 production and, subsequently, TNF-α and IL-6 secretion, tissue remodelling, and fibrosis. The compatibility of the clinical manifestations of COVID-19 with the H4R function pattern further supports this theory. According to the above content, Histamine 4 receptors could be a potential target for COVID-19 treatment. H4R antagonists should be evaluated in experimental in-vitro studies and randomized controlled trials in terms of their therapeutic and preventive effects in COVID-19 complications, severity progression, and mortality.
References
Weiss SR, Leibowitz JL. Coronavirus pathogenesis. Advances in virus research. 81: Elsevier; 2011. 85-164. doi: 10.1016/B978-0-12-385885-6.00009-2, PMid: 22094080, PMCid: PMC7149603 2)Wuhan Municipal Health Commission. Report of clustering pneumonia of unknown etiology in Wuhan City. accessed on 22 January 2020.Available from: http://wjw.wuhan.gov.cn/.
World Health Organization. WHO issues best practices for naming new human infectious diseases. 8 May 2015. Available from: https://www.who.int/news/item/08-05-2015-who-issues-best-practices-for-naming-new-human-infectious-diseases 4)World Health Organization. Surveillance case definitions for human infection with novel coronavirus (nCoV). 15 Jan 2020. Available from: https://www.who.int/publications/m/item/surveillance-case-definitions-for-human-infection-withnovel-coronavirus-(ncov). 5)Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. New England Journal of Medicine. 2020. N Engl J Med 2020; 382:727-733 doi: 10.1056/NEJMoa2001017, PMid: 31978945, PMCid: PMC7092803 6)Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020; 395(10223): 497-506. doi: 10.1016/S0140-6736(20)30183-5 7)World Health Organization. Coronavirus disease 2019 (COVID-19) Situation Report. 4 April 2020. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200404-sitrep-75-covid-19.pdf?sfvrsn=99251b2b_4 8)Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. Jama. 2020; 323(11): 1061-9. doi: 10.1001/jama.2020.1585, PMid: 32031570, PMCid: PMC7042881 9)Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: a retrospective case series study. JAMA Neurol. 2020;77(6):683-690. doi: 10.1101/2020.02.22.20026500 10)Recalcati S. Cutaneous manifestations in COVID‐19: a first perspective. Journal of the European Academy of Dermatology and Venereology. 2020; 34 (5): e212-e213. doi: 10.1111/jdv.16387 11)Henry D, Ackerman M, Sancelme E, Finon A, Esteve E. Urticarial eruption in COVID‐19 infection. Journal of the European Academy of Dermatology and Venereology. 2020; 34 (6): e244-e245. doi: 10.1111/jdv.16472, PMid: 32294273, PMCid: PMC7262133 12)Zhang H, Zhou P, Wei Y, Yue H, Wang Y, Hu M, et al. Histopathologic Changes and SARS–CoV-2 Immunostaining in the Lung of a Patient With COVID-19. Annals of Internal Medicine. 2020; 5;172(9):629-32. doi: 10.7326/L20-0895, PMid: 32805177 13)Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. The Lancet Infectious Diseases. 2020; 20 (4): 425-34, doi: 10.1016/S1473-3099(20)30086-4. 14)Menter T, Haslbauer JD, Nienhold R, Savic S, Hopfer H, Deigendesch N, et al. Postmortem examination ofCOVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020; 77(2):198-209. doi: 10.1111/his.14134, PMid: 32364264, PMCid: PMC7496150 15)Wang J, Wang B, Yang J, Wang M, Chen C, Luo G, et al. Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures. Zhonghua Shao Shang za zhi= Zhonghua Shaoshang Zazhi= Chinese Journal of Burns. 2020;36:E006-E. 16)Xu Y-H, Dong J-H, An W-M, Lv X-Y, Yin X-P, Zhang J-Z, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. Journal of Infection. 2020; 80 (4): 394-400, doi: 10.1016/j.jinf.2020.02.017 17)Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China. Clinical Immunology. 2020: 108393. doi: 10.1016/j.clim.2020.108393, PMid: 32222466, PMCid: PMC7102614 18)Channappanavar R, Perlman S, editors. Pathogenic human coronavirus infections: causes and consequencesof cytokine storm and immunopathology. Seminars in immunopathology; 2017: Springer. doi: 10.1007/s00281-017-0629-x, PMid: 28466096, PMCid: PMC7079893. 39(5):529-539. 19)Conti P, Ronconi G, Caraffa A, Gallenga C, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. Journal of biological regulators and homeostatic agents. 2020; 34(2): 327-31. doi: 10.23812/CONTI-E.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020; 395 (10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3 21)Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive care medicine. 2020; 46(6):1294-1297. doi: 10.1007/s00134-020-06028-z, PMid: 32253449, PMCid: PMC7131986 22)Wu C, Chen X, Cai Y, Zhou X, Xu S, Huang H, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA internal medicine. 2020; 180(7): 934-43. 23)Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020; 71 (15): 762–8. doi: 10.1093/cid/ciaa248. PMid: 32161940, PMCid: PMC7108125 24)Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang Y-Q, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal transduction and targeted therapy. 2020;5(1):1-3.doi: 10.1038/s41392-020-0159-1, PMid: 32377400, PMCid: PMC7189020 25)Liao Y-C, Liang W-G, Chen F-W, Hsu J-H, Yang J-J, Chang M-S. IL-19 induces production of IL-6 and TNF-α and results in cell apoptosis through TNF-α. The Journal of Immunology. 2002;169(8):4288-97. doi: 10.4049/jimmunol.169.8.4288, PMid: 12370360 26)Branco ACCC, Yoshikawa FSY, Pietrobon AJ, Sato MN. Role of histamine in modulating the immune response and inflammation. Mediators of inflammation. 2018; Article IDL 9524075. doi: 10.1155/2018/9524075, PMid: 30224900, PMCid: PMC6129797 27)Kohyama T, Yamauchi Y, Takizawa H, Kamitani S, Kawasaki S, Nagase T. Histamine stimulates human lung fibroblast migration. Molecular and cellular biochemistry. 2010;337(1-2):77-81. doi: 10.1007/s11010-009-0287-y, PMid: 19851834 28)Rosa AC, Pini A, Lucarini L, Lanzi C, Veglia E, Thurmond RL, et al. Prevention of bleomycin-induced lung inflammation and fibrosis in mice by naproxen and JNJ-7777120 treatment. Journal of Pharmacology and Experimental Therapeutics. 2014;351(2):308-16. doi: 10.1124/jpet.114.215152, PMid: 25185215 29)Jemima EA, Prema A, Thangam EB. Functional characterization of histamine H4 receptor on human mast cells. Molecular immunology. 2014;62(1):19-28. doi: 10.1016/j.molimm.2014.05.007, PMid: 24934979 30)Gantner F, Sakai K, Tusche MW, Cruikshank WW, Center DM, Bacon KB. Histamine H4 and H2 receptors control histamine-induced interleukin-16 release from human CD8+ T cells. Journal of Pharmacology and Experimental Therapeutics. 2002;303(1):300-7. doi: 10.1124/jpet.102.036939, PMid: 12235264 31)Durante M, Sgambellone S, Lanzi C, Nardini P, Pini A, MASINI E, et al. Effects of PARP-1 deficiency and histamine H4 receptor inhibition in an inflammatory model of lung fibrosis in mice. Frontiers in pharmacology. 2019;10: 525. doi: 10.3389/fphar.2019.00525, PMid: 31164820, PMCid: PMC6535496 32)Cowden JM, Yu F, Challapalli M, Huang J-F, Kim S, Fung-Leung W-P, et al. Antagonism of the histamine H 4 receptor reduces LPS-induced TNF production in vivo. Inflammation Research. 2013;62(6):599-607. doi: 10.1007/s00011-013-0612-5, PMid: 23532396, PMCid: PMC3654183 33)Morgan RK, McAllister B, Cross L, Green DS, Kornfeld H, Center DM, et al. Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model. The Journal of immunology. 2007; 178(12):8081-9. doi: 10.4049/jimmunol.178.12.8081, PMid: 17548646 34)Gutzmer R, Mommert S, Gschwandtner M, Zwingmann K, Stark H, Werfel T. The histamine H4 receptor is functionally expressed on TH2 cells. Journal of Allergy and Clinical Immunology. 2009;123(3):619-25. doi: 10.1016/j.jaci.2008.12.1110, PMid: 19281909 35)Ahmad SF, Ansari MA, Zoheir KM, Bakheet SA, Korashy HM, Nadeem A, et al. Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. Immunobiology. 2015;220(7):889-98. doi: 10.1016/j.imbio.2015.01.008, PMid: 25666529 36)Chen X, Zhang Z, Dou X, Li J, Zhang W, Yu Y, et al. Histamine H4 Receptor mediates interleukin-; 8 andTNF-α release in human mast cells via multiple signaling pathways. Cellular and Molecular Biology. 2016; 62(1): 84-9. doi: 10.14715/cmb/2016.62.1.16. 37)Shan Y, Gao Y, Zhang L, Ma L, Shi Y, Liu X. H4 Receptor Inhibits Lipopolysaccharide-induced NF-κB Activation by Interacting with Tumor Necrosis Factor Receptor-Associated Factor 6. Neuroscience. 2019;398:113-25. doi: 10.1016/j.neuroscience.2018.11.050, PMid: 30528857
Varga C, Horvath K, Berko A, Thurmond RL, Dunford PJ, Whittle BJ. Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat. European journal of pharmacology. 2005;522(1-3):130-8. doi: 10.1016/j.ejphar.2005.08.045, PMid: 16213481 39)Cowden JM, Zhang M, Dunford PJ, Thurmond RL. The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. Journal of Investigative Dermatology. 2010;130(4):1023-33. doi: 10.1038/jid.2009.358, PMid: 19907432 40)Mommert S, Dittrich-Breiholz O, Stark H, Gutzmer R, Werfel T. The histamine H4 receptor regulates chemokine production in human natural killer cells. International archives of allergy and immunology. 2015;166(3):225-30. doi: 10.1159/000381340, PMid: 25924652 41)Gutzmer R, Diestel C, Mommert S, Köther B, Stark H, Wittmann M, et al. Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. The Journal of Immunology. 2005;174(9):5224-32. doi: 10.4049/jimmunol.174.9.5224, PMid: 15843518 42)Zenewicz LA. IL-22: There is a gap in our knowledge. ImmunoHorizons. 2018;2(6):198-207. doi: 10.4049/immunohorizons.1800006, PMid: 31022687 43)Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. Journal of Microbiology, Immunology and Infection. 2020; 53 (3): 368-70. doi: 10.1016/j.jmii.2020.03.005. 44)Yang D, Chen X, Wang J, Lou Q, Lou Y, Li L, et al. Dysregulated lung commensal bacteria drive interleukin-17B production to promote pulmonary fibrosis through their outer membrane vesicles. Immunity. 2019;50(3):692-706. e7. doi: 10.1016/j.immuni.2019.02.001, PMid: 30824326 45)Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet respiratory medicine. 2020;8(4):420-2. doi: 10.1016/S2213-2600(20)30076-X 46)Faure E, Poissy J, Goffard A, Fournier C, Kipnis E, Titecat M, et al. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside? PloS one. 2014;9(2). doi: 10.1371/journal.pone.0088716, PMid: 24551142, PMCid: PMC3925152 47)Josset L, Menachery VD, Gralinski LE, Agnihothram S, Sova P, Carter VS, et al. Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. MBio. 2013;4(3):e00165-13. doi: 10.1128/mBio.00165-13, PMid: 23631916, PMCid: PMC3663187 48)Li C, Yang P, Sun Y, Li T, Wang C, Wang Z, et al. IL-17 response mediates acute lung injury induced bythe 2009 pandemic influenza A (H1N1) virus. Cell research. 2012;22(3):528-38. doi: 10.1038/cr.2011.165, PMid: 22025253, PMCid: PMC3292301 49)Mommert S, Gschwandtner M, Koether B, Gutzmer R, Werfel T. Human memory Th17 cells express a functional histamine H4 receptor. The American journal of pathology. 2012;180(1):177-85. doi: 10.1016/j.ajpath.2011.09.028, PMid: 22063299 50)Cowden JM, Yu F, Banie H, Farahani M, Ling P, Nguyen S, et al. The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis. Annals of the rheumatic diseases. 2014;73(3):600-8. doi: 10.1136/annrheumdis-2013-203832, PMid: 24126456, PMCid: PMC4151522 51)Cowden JM, Yu F, Banie H, Farahani M, Ling P, Nguyen S, et al. The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis. Ann Rheum Dis. 2014;73(3):600-8. Epub 2013/10/16. doi: 10.1136/annrheumdis-2013-203832. PMID: 24126456; PMCID: PMCPMC4151522. 52)Han SH, Hur MS, Kim MJ, Kim BM, Kim KW, Kim HR, et al. Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis. Journal of dermatological science. 2017;88(1):29-35. doi: 10.1016/j.jdermsci.2017.05.011, PMid: 28592369 53)Tian Y, Rong L, Nian W, He Y. gastrointestinal features in COVID‐19 and the possibility of faecal transmission. Alimentary Pharmacology & Therapeutics. 2020; 51 (9): 843-51. doi: 10.1111/apt.15731, PMid: 32222988, PMCid: PMC7161803 54)Yamamoto K, Okui R, Yamatodani A. Effects of a histamine H4 receptor antagonist on cisplatin-induced anorexia in mice. Neuroscience letters. 2018; 676:103-7. doi: 10.1016/j.neulet.2018.04.019, PMid: 29655943
Schirmer B, Rezniczek T, Seifert R, Neumann D. Proinflammatory role of the histamine H4 receptor in dextrane sodium sulfate-induced acute colitis. Biochemical pharmacology. 2015;98(1):102-9. doi: 10.1016/j.bcp.2015.09.006, PMid: 26365468 56)Dong H, Zhang W, Zeng X, Hu G, Zhang H, He S, et al. Histamine induces upregulated expression of histamine receptors and increases release of inflammatory mediators from microglia. Molecular neurobiology. 2014;49(3):1487-500. doi: 10.1007/s12035-014-8697-6, PMid: 24752587 57)Rocha SM, Pires J, Esteves M, Graça B, Bernardino L. Histamine: a new immunomodulatory player in the neuron-glia crosstalk. Frontiers in cellular neuroscience. 2014;8:120. doi: 10.3389/fncel.2014.00120, PMid: 24817841, PMCid: PMC4012198 58)Zhu J, Qu C, Lu X, Zhang S. Activation of microglia by histamine and substance P. Cellular Physiology and Biochemistry. 2014;34(3):768-80. doi: 10.1159/000363041, PMid: 25170632 59)Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet. 2020; 395 (10239): 1771-8. doi: 10.1016/s0140-6736(20)31103-x. 60)Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet. 2020; 395 (10237): 1607-8. doi: 10.1016/S0140-6736(20)31094-1 61)Lawrensia, S., Henrina, J., Wijaya, E. et al. Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2: a New Challenge amid the Pandemic. SN Compr. Clin. Med. 2020; 2 (10). doi: 10.1007/s42399-020-00602-8 62)Jia S, Li C, Wang G, Yang J, Zu Y. The T helper type 17/regulatory T cell imbalance in patients with acute Kawasaki disease. Clinical & Experimental Immunology. 2010;162(1):131-7. doi: 10.1111/j.1365-2249.2010.04236.x, PMid: 20718783, PMCid: PMC2990938 63)Guo MH, Tseng WN, Ko CH, Pan HM, Hsieh KS, Kuo HC. Th17‐and Treg‐related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease. Allergy. 2015;70(3):310-8. doi: 10.1111/all.12558, PMid: 25585854 64)Rasouli M, Heidari B, Kalani M. Downregulation of Th17 cells and the related cytokines with treatment in Kawasaki disease. Immunology Letters. 2014;162(1):269-75. doi: 10.1016/j.imlet.2014.09.017, PMid: 25277751 65)Boyle DL, DePrimo SE, Calderon C, Chen D, Dunford PJ, Barchuk W, et al. Toreforant, an orally active histamine H(4)-receptor antagonist, in patients with active rheumatoid arthritis despite methotrexate:mechanism of action results from a phase 2, multicenter, randomized, double-blind, placebo-controlled synovial biopsy study. Inflamm Res. 2019;68(4):261-74. Epub 2019/02/11. doi: 10.1007/s00011-019-01218-y. PMID: 30739130. 66)Thurmond RL, Greenspan A, Radziszewski W, Xu XL, Miao Y, Chen B, et al. Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies. J Rheumatol. 2016;43(9):1637-42. Epub 2016/07/17. doi: 10.3899/jrheum.160164. PMID: 27422891.
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