Role of Histamine in Inflammatory Diseases

  • Anette T. Hansen Selnø
  • Vadim V. Sumbayev
  • Ulrike Raap
  • Bernhard F. GibbsEmail author


Histamine plays a major role in inflammation associated with many different diseases, including allergies, autoimmune diseases and cancer, but it also has important physiological effects. Although mast cells and basophils are the main sources of histamine it can be differentially produced and released by enterochromaffin-like cells, certain nerve cells, and even neutrophils in certain pathological settings. This chapter highlights the recent developments regarding the major contributions of histamine to inflammation by acting not only through H1-receptors (H1R) but also H2R and H4R. These receptors determine both the severity of inflammation and also have immunomodulatory effects in various lymphocytes. Recent evidence also suggests a dual role for histamine in various autoimmune inflammatory disease and certain cancers, where differential receptor expressions for the amine determine the severity of these diseases but also play a role in tumour surveillance.


Histamine Mast cells Basophils Allergy Inflammation Cancer 


  1. 1.
    Abd-Allah AR, Ahmad SF, Alrashidi I, Abdel-Hamied HE, Zoheir KM, Ashour AE, Bakheet SA, Attia SM (2014) Involvement of histamine 4 receptor in the pathogenesis and progression of rheumatoid arthritis. Int Immunol 26(6):325–340. CrossRefPubMedGoogle Scholar
  2. 2.
    Adachi N, Liu K, Motoki A, Nishibori M, Arai T (2006) Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats. Eur J Pharmacol 544(1–3):181–187. CrossRefPubMedGoogle Scholar
  3. 3.
    Adams WJ, Lawson JA, Morris DL (1994) Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth. Gut 35(11):1632–1636CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Adlesic M, Verdrengh M, Bokarewa M, Dahlberg L, Foster SJ, Tarkowski A (2007) Histamine in rheumatoid arthritis. Scand J Immunol 65(6):530–537. CrossRefPubMedGoogle Scholar
  5. 5.
    Akamatsu H, Miyachi Y, Asada Y, Niwa Y (1991) Effects of azelastine on neutrophil chemotaxis, phagocytosis and oxygen radical generation. Jpn J Pharmacol 57(4):583–589CrossRefPubMedGoogle Scholar
  6. 6.
    Akin C (2017) Mast cell activation syndromes. J Allergy Clin Immunol 140(2):349–355. CrossRefPubMedGoogle Scholar
  7. 7.
    Albrecht M, Dittrich AM (2015) Expression and function of histamine and its receptors in atopic dermatitis. Mol Cellular Pediatr 2(1):16. CrossRefGoogle Scholar
  8. 8.
    Alcaniz L, Vega A, Chacon P, El Bekay R, Ventura I, Aroca R, Blanca M, Bergstralh DT, Monteseirin J (2013) Histamine production by human neutrophils. FASEB J 27 (7):2902–2910. CrossRefPubMedGoogle Scholar
  9. 9.
    Al-Saadany HM, Hussein MS, Gaber RA, Zaytoun HA (2016) Th-17 cells and serum IL-17 in rheumatoid arthritis patients: correlation with disease activity and severity. Egypt Rheumatol 38(1):1–7. CrossRefGoogle Scholar
  10. 10.
    Ballerini C, Aldinucci A, Luccarini I, Galante A, Manuelli C, Blandina P, Katebe M, Chazot PL, Masini E, Passani MB (2013) Antagonism of histamine H4 receptors exacerbates clinical and pathological signs of experimental autoimmune encephalomyelitis. Br J Pharmacol 170(1):67–77. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Beermann S, Seifert R, Neumann D (2012) Commercially available antibodies against human and murine histamine H(4)-receptor lack specificity. Naunyn Schmiedeberg’s Arch Pharmacol 385(2):125–135. CrossRefGoogle Scholar
  12. 12.
    Betten Å, Dahlgren C, Hermodsson S, Hellstrand K (2003) Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met. Scand J Immunol 58(3):321–326. CrossRefPubMedGoogle Scholar
  13. 13.
    Buckland KF, Williams TJ, Conroy DM (2003) Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J Pharmacol 140(6):1117–1127. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Casale TB, Wood D, Richerson HB, Trapp S, Metzger WJ, Zavala D, Hunninghake GW (1987) Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with methacholine bronchial hyperresponsiveness. J Clin Invest 79(4):1197–1203. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cianchi F, Vinci MC, Masini E (2008) Histamine in cancer: the dual faces of the coin. Cancer Biol Ther 7(1):36–37CrossRefPubMedGoogle Scholar
  16. 16.
    Ciz M, Lojek A (2013) Modulation of neutrophil oxidative burst via histamine receptors. Br J Pharmacol 170(1):17–22. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Clemetson CA (1999) The key role of histamine in the development of atherosclerosis and coronary heart disease. Med Hypotheses 52(1):1–8. CrossRefPubMedGoogle Scholar
  18. 18.
    Constantinescu CS, Farooqi N, O'Brien K, Gran B (2011) Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 164(4):1079–1106. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Cowden JM, Yu F, Banie H, Farahani M, Ling P, Nguyen S, Riley JP, Zhang M, Zhu J, Dunford PJ, Thurmond RL (2014) The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis. Ann Rheum Dis 73(3):600–608. CrossRefPubMedGoogle Scholar
  20. 20.
    Cuapio A, Post M, Cerny-Reiterer S, Gleixner KV, Stefanzl G, Basilio J, Herndlhofer S, Sperr WR, Brons NH, Casanova E, Zimmer J, Valent P, Hofer E (2016) Maintenance therapy with histamine plus IL-2 induces a striking expansion of two CD56bright NK cell subpopulations in patients with acute myeloid leukemia and supports their activation. Oncotarget 7(29):46466–46481. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Cui Y, Hill AW (2016) Atopy and specific cancer sites: a review of epidemiological studies. Clin Rev Allergy Immunol 51(3):338–352. CrossRefPubMedGoogle Scholar
  22. 22.
    De Benedetto A, Yoshida T, Fridy S, Park JE, Kuo IH, Beck LA (2015) Histamine and skin barrier: are histamine antagonists useful for the prevention or treatment of atopic dermatitis? J Clin Med 4(4):741–755. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Deiteren A, De Man JG, Pelckmans PA, De Winter BY (2015) Histamine H(4) receptors in the gastrointestinal tract. Br J Pharmacol 172(5):1165–1178. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    del Rio R, Noubade R, Saligrama N, Wall EH, Krementsov DN, Poynter ME, Zachary JF, Thurmond RL, Teuscher C (2012) Histamine H4 receptor optimizes T regulatory cell frequency and facilitates anti-inflammatory responses within the central nervous system. J Immunol 188 (2):541–547.
  25. 25.
    Delneste Y, Lassalle P, Jeannin P, Joseph M, Tonnel AB, Gosset P (1994) Histamine induces IL-6 production by human endothelial cells. Clin Exp Immunol 98(2):344–349CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Dijkstra D, Leurs R, Chazot P, Shenton FC, Stark H, Werfel T, Gutzmer R (2007) Histamine downregulates monocyte CCL2 production through the histamine H4 receptor. J Allergy Clin Immunol 120(2):300–307. CrossRefPubMedGoogle Scholar
  27. 27.
    Donskov F, Hokland M, Marcussen N, Torp Madsen HH, von der Maase H (2006) Monocytes and neutrophils as 'bad guys' for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma--results from a randomised phase II trial. Br J Cancer 94(2):218–226. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Dy M, Schneider E (2004) Histamine-cytokine connection in immunity and hematopoiesis. Cytokine Growth Factor Rev 15(5):393–410. CrossRefPubMedGoogle Scholar
  29. 29.
    Elenkov IJ, Webster E, Papanicolaou DA, Fleisher TA, Chrousos GP, Wilder RL (1998) Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors. J Immunol 161 (5):2586–2593Google Scholar
  30. 30.
    Emerson MR, Orentas DM, Lynch SG, LeVine SM (2002) Activation of histamine H2 receptors ameliorates experimental allergic encephalomyelitis. Neuroreport 13(11):1407–1410CrossRefPubMedGoogle Scholar
  31. 31.
    Evans HG, Gullick NJ, Kelly S, Pitzalis C, Lord GM, Kirkham BW, Taams LS (2009) In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses. Proc Natl Acad Sci U S A 106(15):6232–6237. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Ezeamuzie CI, Philips E (2000) Histamine H(2) receptors mediate the inhibitory effect of histamine on human eosinophil degranulation. Br J Pharmacol 131(3):482–488. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Fang Z, Yao W, Xiong Y, Li J, Liu L, Shi L, Zhang W, Zhang C, Nie L, Wan J (2011) Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression. BMC Cancer 11(195):191–111. CrossRefGoogle Scholar
  34. 34.
    Faustino-Rocha AI, Ferreira R, Gama A, Oliveira PA, Ginja M (2017) Antihistamines as promising drugs in cancer therapy. Life Sci 172:27–41. CrossRefPubMedGoogle Scholar
  35. 35.
    Felix SB, Baumann G, Helmus S, Sattelberger U (1988) The role of histamine in cardiac anaphylaxis; characterization of histaminergic H1- and H2-receptor effects. Basic Res Cardiol 83(5):531–539CrossRefPubMedGoogle Scholar
  36. 36.
    Flamand N, Plante H, Picard S, Laviolette M, Borgeat P (2004) Histamine-induced inhibition of leukotriene biosynthesis in human neutrophils: involvement of the H2 receptor and cAMP. Br J Pharmacol 141(4):552–561. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Frei R, Ferstl R, Konieczna P, Ziegler M, Simon T, Rugeles TM, Mailand S, Watanabe T, Lauener R, Akdis CA, O'Mahony L (2013) Histamine receptor 2 modifies dendritic cell responses to microbial ligands. J Allergy Clin Immunol 132(1):194–204. CrossRefPubMedGoogle Scholar
  38. 38.
    Fujimoto M, Kimata H (1994) Histamine inhibits immunoglobulin production via histamine H2 receptors without affecting cell growth in human B cells. Clin Immunol Immunopathol 73(1):96–102CrossRefPubMedGoogle Scholar
  39. 39.
    Galkina E, Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis. Annu Rev Immunol 27:165–197. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Galli SJ, Tsai M, Piliponsky AM (2008) The development of allergic inflammation. Nature 454(7203):445–454. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Gantner F, Sakai K, Tusche MW, Cruikshank WW, Center DM, Bacon KB (2002) Histamine h(4) and h(2) receptors control histamine-induced interleukin-16 release from human CD8(+) T cells. J Pharmacol Exp Ther 303(1):300–307. CrossRefPubMedGoogle Scholar
  42. 42.
    Gao C, Major A, Rendon D, Lugo M, Jackson V, Shi Z, Mori-Akiyama Y, Versalovic J (2015) Histamine H2 receptor-mediated suppression of intestinal inflammation by probiotic Lactobacillus reuteri. MBio 6(6):e01358–e01315. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Glatzer F, Gschwandtner M, Ehling S, Rossbach K, Janik K, Klos A, Baumer W, Kietzmann M, Werfel T, Gutzmer R (2013) Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor. J Allergy Clin Immunol 132(6):1358–1367. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Godot V, Arock M, Garcia G, Capel F, Flys C, Dy M, Emilie D, Humbert M (2007) H4 histamine receptor mediates optimal migration of mast cell precursors to CXCL12. J Allergy Clin Immunol 120(4):827–834. doi:S0091-6749(07)01041-X [pii]Google Scholar
  45. 45.
    Gschwandtner M, Mildner M, Mlitz V, Gruber F, Eckhart L, Werfel T, Gutzmer R, Elias PM, Tschachler E (2013) Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy 68(1):37–47. CrossRefPubMedGoogle Scholar
  46. 46.
    Gutzmer R, Langer K, Lisewski M, Mommert S, Rieckborn D, Kapp A, Werfel T (2002) Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells. J Allergy Clin Immunol 109(3):524–531CrossRefPubMedGoogle Scholar
  47. 47.
    Gutzmer R, Diestel C, Mommert S, Kother B, Stark H, Wittmann M, Werfel T (2005) Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. J Immunol 174 (9):5224–5232CrossRefPubMedGoogle Scholar
  48. 48.
    Gutzmer R, Mommert S, Gschwandtner M, Zwingmann K, Stark H, Werfel T (2009) The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol 123(3):619–625. CrossRefPubMedGoogle Scholar
  49. 49.
    Higuchi S, Tanimoto A, Arima N, Xu H, Murata Y, Hamada T, Makishima K, Sasaguri Y (2001) Effects of histamine and interleukin-4 synthesized in arterial intima on phagocytosis by monocytes/macrophages in relation to atherosclerosis. FEBS Lett 505(2):217–222CrossRefPubMedGoogle Scholar
  50. 50.
    Holden NS, Gong W, King EM, Kaur M, Giembycz MA, Newton R (2007) Potentiation of NF-κB-dependent transcription and inflammatory mediator release by histamine in human airway epithelial cells. Br J Pharmacol 152(6):891–902. CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Ikawa Y, Suzuki M, Shiono S, Ohki E, Moriya H, Negishi E, Ueno K (2005) Histamine H4 receptor expression in human synovial cells obtained from patients suffering from rheumatoid arthritis. Biol Pharm Bull 28(10):2016–2018. CrossRefPubMedGoogle Scholar
  52. 52.
    Imaizumi A, Kawakami T, Murakami F, Soma Y, Mizoguchi M (2003) Effective treatment of pruritus in atopic dermatitis using H1 antihistamines (second-generation antihistamines): changes in blood histamine and tryptase levels. J Dermatol Sci 33(1):23–29CrossRefPubMedGoogle Scholar
  53. 53.
    Jadidi-Niaragh F, Mirshafiey A (2010) Histamine and histamine receptors in pathogenesis and treatment of multiple sclerosis. Neuropharmacology 59(3):180–189. CrossRefPubMedGoogle Scholar
  54. 54.
    Jarjour NN, Calhoun WJ, Schwartz LB, Busse WW (1991) Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with increased airway obstruction. Am Rev Respir Dis 144(1):83–87. CrossRefPubMedGoogle Scholar
  55. 55.
    Jemima EA, Prema A, Thangam EB (2014) Functional characterization of histamine H4 receptor on human mast cells. Mol Immunol 62(1):19–28. CrossRefPubMedGoogle Scholar
  56. 56.
    Jutel M, Watanabe T, Klunker S, Akdis M, Thomet OA, Malolepszy J, Zak-Nejmark T, Koga R, Kobayashi T, Blaser K, Akdis CA (2001) Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 413(6854):420–425. CrossRefPubMedGoogle Scholar
  57. 57.
    Kallweit U, Aritake K, Bassetti CL, Blumenthal S, Hayaishi O, Linnebank M, Baumann CR, Urade Y (2013) Elevated CSF histamine levels in multiple sclerosis patients. Fluids and Barriers of the CNS 10:19. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Karouzakis E, Neidhart M, Gay RE, Gay S (2006) Molecular and cellular basis of rheumatoid joint destruction. Immunol Lett 106(1):8–13. CrossRefPubMedGoogle Scholar
  59. 59.
    Kennedy L, Hodges K, Meng F, Alpini G, Francis H (2012) Histamine and histamine receptor regulation of gastrointestinal cancers. Translat Gastrointest Cancer 1(3):215–227Google Scholar
  60. 60.
    Kim KW, Kim BM, Lee KA, Lee SH, Firestein GS, Kim HR (2017) Histamine and histamine H4 receptor promotes osteoclastogenesis in rheumatoid arthritis. Sci Rep 7(1):1197. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Kimata H, Fujimoto M, Ishioka C, Yoshida A (1996) Histamine selectively enhances human immunoglobulin E (IgE) and IgG4 production induced by anti-CD58 monoclonal antibody. J Exp Med 184(2):357–364CrossRefPubMedGoogle Scholar
  62. 62.
    Kimura S, Wang KY, Tanimoto A, Murata Y, Nakashima Y, Sasaguri Y (2004) Acute inflammatory reactions caused by histamine via monocytes/macrophages chronically participate in the initiation and progression of atherosclerosis. Pathol Int 54(7):465–474. CrossRefPubMedGoogle Scholar
  63. 63.
    Kofler HAW, Deibl M, Hawranek TH, Klein G, Reider N, Fellner N (2009) Diamine oxidase (DAO) serum activity: not a useful marker for diagnosis of histamine intolerance. Allergologie 32:105–109CrossRefGoogle Scholar
  64. 64.
    Komericki P, Klein G, Reider N, Hawranek T, Strimitzer T, Lang R, Kranzelbinder B, Aberer W (2011) Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study. Wien Klin Wochenschr 123(1–2):15–20. CrossRefPubMedGoogle Scholar
  65. 65.
    Kubota T, Fujiwara H, Ueda Y, Itoh T, Yamashita T, Yoshimura T, Okugawa K, Yamamoto Y, Yano Y, Yamagishi H (2002) Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients. Br J Cancer 86(8):1257–1261. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Lee SH (2015) Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intest Res 13(1):11–18. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Lieberman P (1990) The use of antihistamines in the prevention and treatment of anaphylaxis and anaphylactoid reactions. J Allergy Clin Immunol 86(4 Pt 2):684–686CrossRefPubMedGoogle Scholar
  68. 68.
    Lin CY, Bai DJ, Yuan HY, Wang K, Yang GL, Hu MB, Wu ZQ, Li Y (2004) Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial. World J Gastroenterol 10(1):136–142. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Ling P, Ngo K, Nguyen S, Thurmond RL, Edwards JP, Karlsson L, Fung-Leung WP (2004) Histamine H4 receptor mediates eosinophil chemotaxis with cell shape change and adhesion molecule upregulation. Br J Pharmacol 142(1):161–171. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Lippert U, Artuc M, Grutzkau A, Babina M, Guhl S, Haase I, Blaschke V, Zachmann K, Knosalla M, Middel P, Kruger-Krasagakis S, Henz BM (2004) Human skin mast cells express H2 and H4, but not H3 receptors. J Invest Dermatol 123(1):116–123. CrossRefPubMedGoogle Scholar
  71. 71.
    MacGlashan D Jr (2003) Histamine: a mediator of inflammation. J Allergy Clin Immunol 112(4 Suppl):S53–S59CrossRefPubMedGoogle Scholar
  72. 72.
    von Mach-Szczypinski J, Stanosz S, Sieja K, Stanosz M (2009) Metabolism of histamine in tissues of primary ductal breast cancer. Metab Clin Exp 58 (6):867–870.
  73. 73.
    Maintz L, Novak N (2007) Histamine and histamine intolerance. Am J Clin Nutr 85(5):1185–1196CrossRefPubMedGoogle Scholar
  74. 74.
    Manzotti G, Breda D, Di Gioacchino M, Burastero SE (2016) Serum diamine oxidase activity in patients with histamine intolerance. Int J Immunopathol Pharmacol 29(1):105–111. CrossRefPubMedGoogle Scholar
  75. 75.
    Martner A, Wiktorin HG, Lenox B, Ewald Sander F, Aydin E, Aurelius J, Thoren FB, Stahlberg A, Hermodsson S, Hellstrand K (2015) Histamine promotes the development of monocyte-derived dendritic cells and reduces tumor growth by targeting the myeloid NADPH oxidase. J Immunol 194(10):5014–5021. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Medina VA, Rivera ES (2010) Histamine receptors and cancer pharmacology. Br J Pharmacol 161(4):755–767. CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Mommert S, Gschwandtner M, Koether B, Gutzmer R, Werfel T (2012) Human memory Th17 cells express a functional histamine H4 receptor. Am J Pathol 180(1):177–185. CrossRefPubMedGoogle Scholar
  78. 78.
    Mommert S, Kleiner S, Gehring M, Eiz-Vesper B, Stark H, Gutzmer R, Werfel T, Raap U (2016) Human basophil chemotaxis and activation are regulated via the histamine H4 receptor. Allergy 71(9):1264–1273. CrossRefPubMedGoogle Scholar
  79. 79.
    Monteseirin J (2009) Neutrophils and asthma. J Investig Allergol Clin Immunol 19(5):340–354PubMedGoogle Scholar
  80. 80.
    Music E, Korosec P, Silar M, Adamic K, Kosnik M, Rijavec M (2013) Serum diamine oxidase activity as a diagnostic test for histamine intolerance. Wien Klin Wochenschr 125(9–10):239–243. CrossRefPubMedGoogle Scholar
  81. 81.
    Nagai Y, Tanaka Y, Kuroishi T, Sato R, Endo Y, Sugawara S (2012) Histamine reduces susceptibility to natural killer cells via down-regulation of NKG2D ligands on human monocytic leukaemia THP-1 cells. Immunology 136(1):103–114. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Nent E, Frommholz D, Gajda M, Brauer R, Illges H (2013) Histamine 4 receptor plays an important role in auto-antibody-induced arthritis. Int Immunol 25(7):437–443. CrossRefPubMedGoogle Scholar
  83. 83.
    Nijmeijer SVH, Sirci F, Schultes S, Engelhardt H, de Graaf C, Rosethorne EM, Charlton SJ, Leurs R (2013) Detailed analysis of biased histamine H4 receptor signalling by JNJ 7777120 analogues. Br J Pharmacol 170:78–88CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Novak N, Mete N, Bussmann C, Maintz L, Bieber T, Akdis M, Zumkehr J, Jutel M, Akdis C (2012) Early suppression of basophil activation during allergen-specific immunotherapy by histamine receptor 2. J Allergy Clin Immunol 130(5):1153–1158. e1152. S0091–6749(12)00715–4 [pii]CrossRefPubMedGoogle Scholar
  85. 85.
    O’Mahony L, Akdis M, Akdis CA (2011) Regulation of the immune response and inflammation by histamine and histamine receptors. J Allergy Clin Immunol 128(6):1153–1162. CrossRefPubMedGoogle Scholar
  86. 86.
    O’Reilly M, Alpert R, Jenkinson S, Gladue RP, Foo S, Trim S, Peter B, Trevethick M, Fidock M (2002) Identification of a histamine H4 receptor on human eosinophils--role in eosinophil chemotaxis. J Recept Signal Transduct Res 22(1–4):431–448. CrossRefPubMedGoogle Scholar
  87. 87.
    Ohki E, Suzuki M, Aoe T, Ikawa Y, Negishi E, Ueno K (2007) Expression of histamine H4 receptor in synovial cells from rheumatoid arthritic patients. Biol Pharm Bull 30(11):2217–2220. CrossRefPubMedGoogle Scholar
  88. 88.
    Ohsawa Y, Hirasawa N (2014) The role of histamine H1 and H4 receptors in atopic dermatitis: from basic research to clinical study. Allergol Int 63(4):533–542. CrossRefPubMedGoogle Scholar
  89. 89.
    Passani MB, Ballerini C (2012) Histamine and neuroinflammation: insights from murine experimental autoimmune encephalomyelitis. Front Syst Neurosci 6.
  90. 90.
    Peavy RD, Metcalfe DD (2008) Understanding the mechanisms of anaphylaxis. Curr Opin Allergy Clin Immunol 8(4):310–315. CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Phanuphak P, Schocket AL, Arroyave CM, Kohler PF Skin histamine in chronic urticaria. J Allergy Clin Immunol 65(5):371–375. CrossRefPubMedGoogle Scholar
  92. 92.
    Qu YL, Liu J, Zhang LX, Wu CM, Chu AJ, Wen BL, Ma C, Yan XY, Zhang X, Wang DM, Lv X, Hou SJ (2017) Asthma and the risk of lung cancer: a meta-analysis. Oncotarget.
  93. 93.
    Reese I, Ballmer-Weber B, Beyer K, Fuchs T, Kleine-Tebbe J, Klimek L, Lepp U, Niggemann B, Saloga J, Schafer C, Werfel T, Zuberbier T, Worm M (2017) German guideline for the management of adverse reactions to ingested histamine: guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Association of Allergologists (AeDA), and the Swiss Society for Allergology and Immunology (SGAI). Allergo J Int 26(2):72–79. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Rigoni A, Colombo MP, Pucillo C (2015) The role of mast cells in molding the tumor microenvironment. Cancer Microenviron 8(3):167–176. CrossRefPubMedGoogle Scholar
  95. 95.
    Sander LE, Lorentz A, Sellge G, Coëffier M, Neipp M, Veres T, Frieling T, Meier PN, Manns MP, Bischoff SC (2006) Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract. Gut 55(4):498–504. CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Sasaguri Y, Tanimoto A (2004) Role of macrophage-derived histamine in atherosclerosis-- chronic participation in the inflammatory response. J Atheroscler Thromb 11(3):122–130CrossRefPubMedGoogle Scholar
  97. 97.
    Schneider EH, Seifert R (2016) The histamine H4-receptor and the central and peripheral nervous system: A critical analysis of the literature. Neuropharmacology 106:116–128. CrossRefPubMedGoogle Scholar
  98. 98.
    Schneider E, Machavoine F, Pléau JM, Bertron AF, Thurmond RL, Ohtsu H, Watanabe T, Schinkel AH, Dy M (2005) Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels. J Exp Med 202(3):387–393. CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Schneider E, Machavoine F, Bricard-Rignault R, Levasseur M, Petit-Bertron AF, Gautron S, Ribeil JA, Launay JM, Mecheri S, Cote F, Dy M (2011) Downregulation of basophil-derived IL-4 and in vivo T(H)2 IgE responses by serotonin and other organic cation transporter 3 ligands. J Allergy Clin Immunol 128(4):864–871.e862. CrossRefPubMedGoogle Scholar
  100. 100.
    Schnoor HS, Mosbech H, Skov PS, Poulsen LK, Jensen BM (2013) Diamine oxidase determination in serum. Allergo J 22:108–111CrossRefGoogle Scholar
  101. 101.
    Seifert R, Strasser A, Schneider EH, Neumann D, Dove S, Buschauer A (2013) Molecular and cellular analysis of human histamine receptor subtypes. Trends Pharmacol Sci 34(1):33–58. CrossRefPubMedGoogle Scholar
  102. 102.
    Smolinska S, Jutel M, Crameri R, O'Mahony L (2014) Histamine and gut mucosal immune regulation. Allergy 69(3):273–281. CrossRefPubMedGoogle Scholar
  103. 103.
    Smolinska S, Groeger D, Perez NR, Schiavi E, Ferstl R, Frei R, Konieczna P, Akdis CA, Jutel M, O'Mahony L (2016) Histamine receptor 2 is required to suppress innate immune responses to bacterial ligands in patients with inflammatory bowel disease. Inflamm Bowel Dis 22(7):1575–1586. CrossRefPubMedGoogle Scholar
  104. 104.
    Styrt B, Rocklin RE, Klempner MS (1988) Characterization of the neutrophil respiratory burst in atopy. J Allergy Clin Immunol 81(1):20–26CrossRefPubMedGoogle Scholar
  105. 105.
    Takagishi T, Sasaguri Y, Nakano R, Arima N, Tanimoto A, Fukui H, Morimatsu M (1995) Expression of the histamine H1 receptor gene in relation to atherosclerosis. Am J Pathol 146(4):981–988PubMedPubMedCentralGoogle Scholar
  106. 106.
    Teuscher C, Poynter ME, Offner H, Zamora A, Watanabe T, Fillmore PD, Zachary JF, Blankenhorn EP (2004) Attenuation of Th1 effector cell responses and susceptibility to experimental allergic encephalomyelitis in histamine H2 receptor knockout mice is due to dysregulation of cytokine production by antigen-presenting cells. Am J Pathol 164(3):883–892. CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Thurmond RL, Gelfand EW, Dunford PJ (2008) The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 7(1):41–53. CrossRefPubMedGoogle Scholar
  108. 108.
    Triggiani M, Petraroli A, Loffredo S, Frattini A, Granata F, Morabito P, Staiano RI, Secondo A, Annunziato L, Marone G (2007) Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor. J Allergy Clin Immunol 119(2):472–481. CrossRefPubMedGoogle Scholar
  109. 109.
    Truta-Feles K, Lagadari M, Lehmann K, Berod L, Cubillos S, Piehler S, Herouy Y, Barz D, Kamradt T, Maghazachi A, Norgauer J (2010) Histamine modulates gammadelta-T lymphocyte migration and cytotoxicity, via Gi and Gs protein-coupled signalling pathways. Br J Pharmacol 161(6):1291–1300. CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Vannier E, Miller LC, Dinarello AC (1991) Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors. J Exp Med 174(1):281–284CrossRefPubMedGoogle Scholar
  111. 111.
    Vila-Leahey A, Rogers D, Marshall JS (2016) The impact of ranitidine on monocyte responses in the context of solid tumors. Oncotarget 7(10):10891–10904. CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Wang KY, Arima N, Higuchi S, Shimajiri S, Tanimoto A, Murata Y, Hamada T, Sasaguri Y (2000) Switch of histamine receptor expression from H2 to H1 during differentiation of monocytes into macrophages. FEBS Lett 473(3):345–348CrossRefPubMedGoogle Scholar
  113. 113.
    Wantke F, Proud D, Siekierski E, Kagey-Sobotka A (1998) Daily variations of serum diamine oxidase and the influence of H1 and H2 blockers: a critical approach to routine diamine oxidase assessment. Inflamm Res 47(10):396–400. CrossRefPubMedGoogle Scholar
  114. 114.
    Wolff AA, Levi R (1986) Histamine and cardiac arrhythmias. Circ Res 58(1):1–16CrossRefPubMedGoogle Scholar
  115. 115.
    Yang LP, Perry CM (2011) Spotlight on histamine dihydrochloride in acute myeloid leukaemia. Drugs Aging 28(4):325–329. CrossRefPubMedGoogle Scholar
  116. 116.
    Yang XD, Ai W, Asfaha S, Bhagat G, Friedman RA, Jin G, Park H, Shykind B, Diacovo TG, Falus A, Wang TC (2011) Histamine deficiency promotes inflammation-associated carcinogenesis through reduced myeloid maturation and accumulation of CD11b+Ly6G+ immature myeloid cells. Nat Med 17:87–95CrossRefPubMedGoogle Scholar
  117. 117.
    Zampeli E, Tiligada E (2009) The role of histamine H4 receptor in immune and inflammatory disorders. Br J Pharmacol 157(1):24–33. CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Zappulla JP, Arock M, Mars LT, Liblau RS (2002) Mast cells: new targets for multiple sclerosis therapy? J Neuroimmunol 131(1–2):5–20CrossRefPubMedGoogle Scholar
  119. 119.
    Musio S, Gallo B, Scabeni S, Lapilla M, Poliani PL, Matarese G, Ohtsu H, Galli SJ, Mantegazza R, Steinman L, Pedotti R (2006) A key regulatory role for histamine in experimental autoimmune encephalomyelitis: disease exacerbation in histidine decarboxylase-deficient mice. J Immunol 176(1):17–26CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Anette T. Hansen Selnø
    • 1
  • Vadim V. Sumbayev
    • 1
  • Ulrike Raap
    • 2
  • Bernhard F. Gibbs
    • 2
    Email author
  1. 1.School of PharmacyUniversity of KentKentUK
  2. 2.Faculty of Medicine and Health Sciences (Dermatology, W16), Department of Dermatology and AllergyUniversity of OldenburgOldenburgGermany

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