Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Nov;98(2):344–349. doi: 10.1111/j.1365-2249.1994.tb06148.x

Histamine induces IL-6 production by human endothelial cells.

Y Delneste 1, P Lassalle 1, P Jeannin 1, M Joseph 1, A B Tonnel 1, P Gosset 1
PMCID: PMC1534408  PMID: 7955543

Abstract

Histamine is one of the major mediators implicated in the physiopathology of allergy. On vascular endothelium, histamine mainly induces early effects: an increase in vasopermeability leading to oedema, a release of lipid mediators and a transient expression of P-selectin. The aim of this study was to evaluate the effects of histamine on adhesion molecule expression and IL-6 production by human endothelial cells. Histamine did not modulate the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, but induced a transient expression of P-selectin as previously reported. In addition, histamine increased in a dose- (from 10(-5) to 10(-3) M) and time- (from 4 h to 24 h) dependent fashion the IL-6 synthesis by endothelial cells. Tumour necrosis factor-alpha (TNF-alpha)-induced IL-6 production was also potentiated in a dose-dependent manner by histamine, without modification of the time course of IL-6 secretion. Moreover, this increase of IL-6 production induced by histamine was inhibited in a dose-dependent manner by H1 and H2 histamine receptor antagonists (50% inhibition of IL-6 production at 5 x 10(-4) M and 4 x 10(-5) M, respectively). So, histamine induces, besides already well known effects, a late stimulation of endothelial cells, i.e. the production of IL-6.

Full text

PDF

Images in this article

347Fig. 3
on p.347

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Azzawi M., Bradley B., Jeffery P. K., Frew A. J., Wardlaw A. J., Knowles G., Assoufi B., Collins J. V., Durham S., Kay A. B. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1407–1413. doi: 10.1164/ajrccm/142.6_Pt_1.1407. [DOI] [PubMed] [Google Scholar]
  2. Baenziger N. L., Force L. E., Becherer P. R. Histamine stimulate prostacyclin synthesis in cultured human umbilical vein endothelial cells. Biochem Biophys Res Commun. 1980 Feb 27;92(4):1435–1440. doi: 10.1016/0006-291x(80)90447-7. [DOI] [PubMed] [Google Scholar]
  3. Barnes P. J. Histamine receptors in the lung. Agents Actions Suppl. 1991;33:103–122. doi: 10.1007/978-3-0348-7309-3_9. [DOI] [PubMed] [Google Scholar]
  4. Casale T. B., Wood D., Richerson H. B., Trapp S., Metzger W. J., Zavala D., Hunninghake G. W. Elevated bronchoalveolar lavage fluid histamine levels in allergic asthmatics are associated with methacholine bronchial hyperresponsiveness. J Clin Invest. 1987 Apr;79(4):1197–1203. doi: 10.1172/JCI112937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Choi I., Kang H. S., Yang Y., Pyun K. H. IL-6 induces hepatic inflammation and collagen synthesis in vivo. Clin Exp Immunol. 1994 Mar;95(3):530–535. doi: 10.1111/j.1365-2249.1994.tb07031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Falus A., Merétey K. Histamine: an early messenger in inflammatory and immune reactions. Immunol Today. 1992 May;13(5):154–156. doi: 10.1016/0167-5699(92)90117-p. [DOI] [PubMed] [Google Scholar]
  7. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Geng J. G., Bevilacqua M. P., Moore K. L., McIntyre T. M., Prescott S. M., Kim J. M., Bliss G. A., Zimmerman G. A., McEver R. P. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature. 1990 Feb 22;343(6260):757–760. doi: 10.1038/343757a0. [DOI] [PubMed] [Google Scholar]
  9. Gosset P., Malaquin F., Delneste Y., Wallaert B., Capron A., Joseph M., Tonnel A. B. Interleukin-6 and interleukin-1 alpha production is associated with antigen-induced late nasal response. J Allergy Clin Immunol. 1993 Dec;92(6):878–890. doi: 10.1016/0091-6749(93)90066-o. [DOI] [PubMed] [Google Scholar]
  10. Gosset P., Tsicopoulos A., Wallaert B., Joseph M., Capron A., Tonnel A. B. Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. Am Rev Respir Dis. 1992 Sep;146(3):768–774. doi: 10.1164/ajrccm/146.3.768. [DOI] [PubMed] [Google Scholar]
  11. Gosset P., Tsicopoulos A., Wallaert B., Vannimenus C., Joseph M., Tonnel A. B., Capron A. Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol. 1991 Oct;88(4):561–571. doi: 10.1016/0091-6749(91)90149-i. [DOI] [PubMed] [Google Scholar]
  12. Hill S. J. Multiple histamine receptors: properties and functional characteristics. Biochem Soc Trans. 1992 Feb;20(1):122–125. doi: 10.1042/bst0200122. [DOI] [PubMed] [Google Scholar]
  13. Hogg J. C. The pathology of asthma. Clin Chest Med. 1984 Dec;5(4):567–571. [PubMed] [Google Scholar]
  14. Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jirik F. R., Podor T. J., Hirano T., Kishimoto T., Loskutoff D. J., Carson D. A., Lotz M. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol. 1989 Jan 1;142(1):144–147. [PubMed] [Google Scholar]
  16. Kishimoto T. The biology of interleukin-6. Blood. 1989 Jul;74(1):1–10. [PubMed] [Google Scholar]
  17. Kopf M., Baumann H., Freer G., Freudenberg M., Lamers M., Kishimoto T., Zinkernagel R., Bluethmann H., Köhler G. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature. 1994 Mar 24;368(6469):339–342. doi: 10.1038/368339a0. [DOI] [PubMed] [Google Scholar]
  18. Lee C. E., Neuland M. E., Teaford H. G., Villacis B. F., Dixon P. S., Valtier S., Yeh C. H., Fournier D. C., Charlesworth E. N. Interleukin-6 is released in the cutaneous response to allergen challenge in atopic individuals. J Allergy Clin Immunol. 1992 May;89(5):1010–1020. doi: 10.1016/0091-6749(92)90224-p. [DOI] [PubMed] [Google Scholar]
  19. Leeuwenberg J. F., von Asmuth E. J., Jeunhomme T. M., Buurman W. A. IFN-gamma regulates the expression of the adhesion molecule ELAM-1 and IL-6 production by human endothelial cells in vitro. J Immunol. 1990 Oct 1;145(7):2110–2114. [PubMed] [Google Scholar]
  20. Locksley R. M., Heinzel F. P., Shepard H. M., Agosti J., Eessalu T. E., Aggarwal B. B., Harlan J. M. Tumor necrosis factors alpha and beta differ in their capacities to generate interleukin 1 release from human endothelial cells. J Immunol. 1987 Sep 15;139(6):1891–1895. [PubMed] [Google Scholar]
  21. Lorant D. E., Patel K. D., McIntyre T. M., McEver R. P., Prescott S. M., Zimmerman G. A. Coexpression of GMP-140 and PAF by endothelium stimulated by histamine or thrombin: a juxtacrine system for adhesion and activation of neutrophils. J Cell Biol. 1991 Oct;115(1):223–234. doi: 10.1083/jcb.115.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. MAJNO G., PALADE G. E. Studies on inflammation. 1. The effect of histamine and serotonin on vascular permeability: an electron microscopic study. J Biophys Biochem Cytol. 1961 Dec;11:571–605. doi: 10.1083/jcb.11.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mantovani A., Bussolino F., Dejana E. Cytokine regulation of endothelial cell function. FASEB J. 1992 May;6(8):2591–2599. doi: 10.1096/fasebj.6.8.1592209. [DOI] [PubMed] [Google Scholar]
  24. Moutabarrik A., Ishibashi M., Namiki M., Kameoka H., Kokado Y., Yoshizaki K., Takano Y., Yokokawa K., Takahara S., Seguchi T. Disparate regulation of interleukin-6 secretion from blood monocytes and vascular endothelial cells by interleukin-4. Transplant Proc. 1992 Dec;24(6):2898–2899. [PubMed] [Google Scholar]
  25. Muraguchi A., Hirano T., Tang B., Matsuda T., Horii Y., Nakajima K., Kishimoto T. The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988 Feb 1;167(2):332–344. doi: 10.1084/jem.167.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Naclerio R. M., Proud D., Togias A. G., Adkinson N. F., Jr, Meyers D. A., Kagey-Sobotka A., Plaut M., Norman P. S., Lichtenstein L. M. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med. 1985 Jul 11;313(2):65–70. doi: 10.1056/NEJM198507113130201. [DOI] [PubMed] [Google Scholar]
  27. Naclerio R. M. The role of histamine in allergic rhinitis. J Allergy Clin Immunol. 1990 Oct;86(4 Pt 2):628–632. doi: 10.1016/s0091-6749(05)80227-1. [DOI] [PubMed] [Google Scholar]
  28. Noah T. L., Paradiso A. M., Madden M. C., McKinnon K. P., Devlin R. B. The response of a human bronchial epithelial cell line to histamine: intracellular calcium changes and extracellular release of inflammatory mediators. Am J Respir Cell Mol Biol. 1991 Nov;5(5):484–492. doi: 10.1165/ajrcmb/5.5.484. [DOI] [PubMed] [Google Scholar]
  29. Ottosson A., Jansen I., Edvinsson L. Pharmacological characterization of histamine receptors in the human temporal artery. Br J Clin Pharmacol. 1989 Feb;27(2):139–145. doi: 10.1111/j.1365-2125.1989.tb05344.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Plaut M., Pierce J. H., Watson C. J., Hanley-Hyde J., Nordan R. P., Paul W. E. Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. Nature. 1989 May 4;339(6219):64–67. doi: 10.1038/339064a0. [DOI] [PubMed] [Google Scholar]
  31. Rafferty P., Holgate S. T. Histamine and its antagonists in asthma. J Allergy Clin Immunol. 1989 Aug;84(2):144–151. doi: 10.1016/0091-6749(89)90317-5. [DOI] [PubMed] [Google Scholar]
  32. Robinson D. S., Hamid Q., Ying S., Tsicopoulos A., Barkans J., Bentley A. M., Corrigan C., Durham S. R., Kay A. B. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992 Jan 30;326(5):298–304. doi: 10.1056/NEJM199201303260504. [DOI] [PubMed] [Google Scholar]
  33. Strieter R. M., Kunkel S. L., Showell H. J., Remick D. G., Phan S. H., Ward P. A., Marks R. M. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. doi: 10.1126/science.2648570. [DOI] [PubMed] [Google Scholar]
  34. Söderberg M., Lundgren R., Bjermer L., Stjernberg N., Rosenhall L. Inflammatory response in bronchoalveolar lavage fluid after inhaling histamine. Allergy. 1989 Feb;44(2):98–102. doi: 10.1111/j.1398-9995.1989.tb02231.x. [DOI] [PubMed] [Google Scholar]
  35. Van Snick J., Cayphas S., Vink A., Uyttenhove C., Coulie P. G., Rubira M. R., Simpson R. J. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679–9683. doi: 10.1073/pnas.83.24.9679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vannier E., Dinarello C. A. Histamine enhances interleukin (IL)-1-induced IL-1 gene expression and protein synthesis via H2 receptors in peripheral blood mononuclear cells. Comparison with IL-1 receptor antagonist. J Clin Invest. 1993 Jul;92(1):281–287. doi: 10.1172/JCI116562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Varney V. A., Jacobson M. R., Sudderick R. M., Robinson D. S., Irani A. M., Schwartz L. B., Mackay I. S., Kay A. B., Durham S. R. Immunohistology of the nasal mucosa following allergen-induced rhinitis. Identification of activated T lymphocytes, eosinophils, and neutrophils. Am Rev Respir Dis. 1992 Jul;146(1):170–176. doi: 10.1164/ajrccm/146.1.170. [DOI] [PubMed] [Google Scholar]
  38. White M. V. The role of histamine in allergic diseases. J Allergy Clin Immunol. 1990 Oct;86(4 Pt 2):599–605. doi: 10.1016/s0091-6749(05)80223-4. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES