Journal of Clinical Immunology

, Volume 16, Issue 1, pp 31–40 | Cite as

Mercury-specific lymphocytes: An indication of mercury allergy in man

  • Vera D. M. Stejskal
  • Margit Forsbeck
  • Karin E. Cederbrant
  • Ola Asteman
Original Articles

Abstract

In this study, 18 patients with oral lichen planus (OLP), adjacent to amalgam fillings, were testedin vitro with an optimized lymphocyte proliferation test, MELISA (memory lymphocyte immunostimulation assay) and with a patch test. Twenty subjects with amalgam fillings but without oral discomfort and 12 amalgam-free subjects served as controls. The results show that patients with OLP have significantly higher lymphocyte reactivity to inorganic mercury, a corrosion product of amalgam, compared to control groups. Removal of amalgam fillings resulted in the disappearance of oral mucosal changes, thus indicating a causal relationship. Positive responses to phenylmercury (phenyl-Hg), a bactericidal agent in rootfillings and in pharmaceutical preparations, were also noted in the oral lichen group but not in the control groups. Thus, low-grade chronic exposure to mercury may induce a state of systemic sensitization as verified by Hg-specific lymphocyte reactivityin vitro.

Key words

Cell-mediated immunity silver amalgam mercury human memory lymphocytes MELISA 

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References

  1. 1.
    Goering PL, Galloway WD, Clarkson TW, Lorscheider FL, Berlin M, Rowland AS: Symposium overview, toxicity assessment of mercury vapor from dental amalgams. Fund Appl Toxicol 19:319–329, 1992Google Scholar
  2. 2.
    Eneström S, Hultman P: Does amalgam affect the immune system? A controversial issue. Int Arch Allergy Immunol 106:180–203, 1995PubMedGoogle Scholar
  3. 3.
    Chang LW: Neurotoxic effects of mercury—A review. Environ Res 14:329–373, 1977PubMedGoogle Scholar
  4. 4.
    Kazantzis G: The role of hypersensitivity and the immune response in influencing susceptibility to metal toxicity. Environ Health Perspect 25:111–118, 1978PubMedGoogle Scholar
  5. 5.
    Hultman P, Johansson U, Turley SJ, Lindh U, Eneström S, Pollard KM: Adverse immunological effects and autoimmunity induced by dental amalgam and alloy in mice. FASEB J 8:1183–1190, 1994PubMedGoogle Scholar
  6. 6.
    Stejskal VDM, Olin RG, Forsbeck M: The lymphocyte transformation test for diagnosis of drug-induced occupational allergy. J Allergy Clin Immunol 77:411–426, 1986PubMedGoogle Scholar
  7. 7.
    Stejskal VDM: Allergy to drugs and other chemicals diagnosed by the presence of specific memory cells in human blood.In Realm of Tolerance, Ivanyi P (eds). Berlin, New York, London, Springer-Verlag 1989, pp 213–224Google Scholar
  8. 8.
    Stejskal VDM, Forsbeck M, Nilsson R: Lymphocyte transformation test for diagnosis of isothiazolinone allergy in man. J Invest Dermatol 94:798–802, 1990PubMedGoogle Scholar
  9. 9.
    Jolly M, Moule AJ, Freeman S: Amalgam-related chronic ulceration of oral mucosa. Br Dent J 160:434–437, 1986PubMedGoogle Scholar
  10. 10.
    James J, Ferguson MM, Forsyth A, Tulloch N, Lamey PJ: Oral lichenoid reactions related to mercury sensitivity. Br J Oral Maxillofac Surg 25:474–480, 1987PubMedGoogle Scholar
  11. 11.
    Laine J, Kalimo K, Forssell H, Happonen RP: Resolution of oral lichenoid lesions after replacement of amalgam fillings in patients allergic to mercury compounds. Br J Dermatol 126:10–15, 1992PubMedGoogle Scholar
  12. 12.
    Stejskal VDM, Cederbrant K, Lindvall A, Forsbeck M: MEL-ISA—Anin vitro tool for the study of metal allergy. Toxicol In Vitro 8:991–1000, 1994Google Scholar
  13. 13.
    Pirilä V: Chamber testing versus patch test for epicutanous testing. Contact Derm 1:48–52, 1975PubMedGoogle Scholar
  14. 14.
    Hutchinson F, Raffle EJ, Macleod TM: The specificity of lymphocyte transformation in vitro by nickel salts in nickel sensitive subjects. J Invest Dermatol 58:362–365, 1972PubMedGoogle Scholar
  15. 15.
    Kreiss K, Newman LS, Mroz MM, Campbell PA: Screening blood test identifies subclinical beryllium disease. J Occup Med 31:603–608, 1989PubMedGoogle Scholar
  16. 16.
    Denman EJ, Denman AM: The lymphocyte transformation test and gold hypersensitivity. Ann Rheum Dis 27:582–589, 1968PubMedGoogle Scholar
  17. 17.
    Kubicka-Muranyi M, Behmer O, Uhrberg M, Klonowski H, Bister J, Gleichmann E: Murine systemic autoimmune disease induced by mercuric chloride (HgCl2): Hg-specific helper T-cells react to antigen stored in macrophages. Int J Immunopharm 15:151–161, 1993Google Scholar
  18. 18.
    Walker DM: The inflammatory infiltrate in lichen planus lesions. An autoradiographic and ultrastructural study. J Oral Pathol 5:277–286, 1976PubMedGoogle Scholar
  19. 19.
    Regezi JA, Deegan MJ, Hayward JR: Lichen planus: Immunologic and morphologic identification of the submucosal infiltrate. Oral Surg 46:44–52, 1978PubMedGoogle Scholar
  20. 20.
    Bircher AJ, von Schulthess A, Henning G: Oral lichoid lesions and mercury sensitivity. Contact Derm 29:275–276, 1993PubMedGoogle Scholar
  21. 21.
    Finne K, Göransson K, Winckler L: OLP and contact allergy to mercury. Int J Oral Surg 11:236–239, 1982PubMedGoogle Scholar
  22. 22.
    Lundström IMC: Allergy and corrosion of dental materials in patients with OLP. Int J Oral Surg 13:16–24, 1984PubMedGoogle Scholar
  23. 23.
    Tigelaar RE, Bergstresser PR, Lonsberry LM, Elmets C, Wood PJ, Streilein JW: Oral ingestion of epicutaneously applied hapten in mice may unwittingly induce down-regulation of contact hypersensitivity. J Immunol 129:1898–1904, 1982PubMedGoogle Scholar
  24. 24.
    Vreeburg KJ, de Groot K, von Blomberg M, Scheper RJ: Induction of immunological tolerance by oral administration of nickel and chromium. J Dent Res 63:124–128, 1984PubMedGoogle Scholar
  25. 25.
    Bolewska J, Holmstrup P, Möller-Madsen B, Kenrad B, Danscher G: Amalgam associated mercury accumulations in normal oral mucosa, oral mucosal lesions of lichen planus and contact lesions associated with amalgam. J Oral Pathol Med 19:39–42, 1990PubMedGoogle Scholar
  26. 26.
    Williams DF: Biocompatibility of Implant Materials. London, Pitmans Medical, 1976Google Scholar
  27. 27.
    Williams DF: Fundamental Aspects of Biocompatibility II: CRC Series in Biocompatibility. Boca Raton, FL, CRC Press, 1981Google Scholar
  28. 28.
    Buchner A, Hansen LS: Amalgam pigmentation (amalgam tattoo) of the oral mucosa. A clinicopathologic study of 268 cases. Oral Surg 49:139–147, 1980PubMedGoogle Scholar
  29. 29.
    Nakayama H, Niki F, Shono M, Hada S: Mercury exanthem. Contact Derm 9:411–417, 1983PubMedGoogle Scholar
  30. 30.
    Young E: Ammoniated mercury poisoning. Br J Dermatol 72:449–455, 1960PubMedGoogle Scholar
  31. 31.
    Mathews KP, Pan PM: Immediate type hypersensitivity to phenylmercuric compounds. Am J Med 44:310–318, 1968PubMedGoogle Scholar
  32. 32.
    Block RM, Sheats JB, Denby Lewis R, Fawley J: Cell-mediated immune response to dog pulp tissue altered by N2 paste within the root canal. Oral Surg 45:131–142, 1978PubMedGoogle Scholar
  33. 33.
    Höök O, Lundgren K-D, Swensson Å: On alkyl mercury poisoning. Acta Med Scand CL(II):131–137, 1954Google Scholar
  34. 34.
    Jalili MA, Abbasi AH: Poisoning by ethyl mercury toluene sulphonanilide. Br J Ind Med 18:303–308, 1961PubMedGoogle Scholar
  35. 35.
    Möller H: Merthiolate allergy: A nationwide iatrogenic sensitization. Acta Dermatol 57:509–517, 1977Google Scholar
  36. 36.
    Pirker C, Möslinger T, Wantke F, Götz M, Jarisch R: Ethylmercuric chloride: The responsible agent in Thimerosal hypersensitivity. Contact Derm 29:152–154, 1993PubMedGoogle Scholar
  37. 37.
    Ellis FA, Robinson HM: Cutaneous sensitivity to merthiolate and other mercurial compounds. Arch Dermat Syph 46:425–430, 1942Google Scholar
  38. 38.
    von Mayenburg J, Rakoski J, Szliska C: Patch testing with amalgam at various concentrations. Contact Derm 24:266–269, 1991PubMedGoogle Scholar
  39. 39.
    Schöpf E, Schulz KH, Gromm M: Transformation und Mitosen von Lymphocyten in vitro durch Quecksilber(11)-chlorid. Naturwissenschaften 54:568, 1967Google Scholar
  40. 40.
    Caron GA, Poutala S, Provost TT: Lymphocyte transformation induced by inorganic and organic mercury. Int Arch Allergy 37:76–87, 1970PubMedGoogle Scholar
  41. 41.
    Nordlind K, Liden S: In vitro lymphocyte reactivity to heavy metal salts in the diagnosis of oral mucosal hypersensitivity to amalgam fillings. Br J Dermatol 128:38–41, 1993PubMedGoogle Scholar
  42. 42.
    FDA, National Centre for Devices and Radiological Health, Device Monitoring Branch: Device Experience Network Monthly Report 8:11–12, 1983Google Scholar
  43. 43.
    Wylie DE, Lu D, Carlson LD: Monoclonal antibodies specific for mercuric ions. Proc Natl Acad Sci USA 89:4104–4108, 1992PubMedGoogle Scholar
  44. 44.
    Dayan AD, Hertd RF, Heseltine E, Kazantzis G, Smith EM, Van der Venne MT: Immunotoxicology of metals and immunotoxicology. Proceedings of an International Workshop, IPCS Joint Symposia No. 15. New York, London, Plenum Press, 1990Google Scholar
  45. 45.
    Goldman M, Druet P, Gleichmann E: TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemicallyinduced autoimmunity. Immunol Today 12:223–226, 1991PubMedGoogle Scholar
  46. 46.
    Jontell M, Ståhlblad PÅ, Rosdahl I, Lindblom B: HLA-DR3 antigens in erosive oral lichen planus, cutaneous lichen planus, and lichenoid reactions. Acta Odontol Scand 45:309–312, 1987PubMedGoogle Scholar
  47. 47.
    Van Der Horst JC, Cirkel PKS, Nieboer C: Mixed lichen planuslupus erythematosus disease: a distinct entity? Clinical, histopathological and immunopathological studies in six patients. Clin Exp Dermatol 8:631–640, 1983PubMedGoogle Scholar
  48. 48.
    Brennum J, Hjelt K: Mb Crohn diagnostiseret ved oral biopsi fra afte. Nord Med 101:131, 1986PubMedGoogle Scholar
  49. 49.
    Wyatt EH: Lichen planus and ulcerative colitis. Br J Dermatol 93:465–468, 1975PubMedGoogle Scholar
  50. 50.
    Jolly M: Lichen planus and its association with diabetes mellitus. Med J Aust 1:990–992, 1972PubMedGoogle Scholar
  51. 51.
    Schrallhammer-Benkler K, Ring J, Meurer PM, Landthaler M: Acute mercury intoxication with lichenoid drug eruption followed by mercury contact allergy and development of antinuclear antibodies. Acta Derm Venereol 72:294–296, 1992PubMedGoogle Scholar
  52. 52.
    Tibbling L, Thuomas KÅ, Lenkei R, Stejskal VDM: Immunological and brain MRI changes in patients with suspected metal intoxication. Int J Occupat Med Toxicol 4:1–10, 1995Google Scholar
  53. 53.
    Danscher G, Horsted-Bindslew P, Rungby J: Traces of mercury in organs from primates with amalgam fillings. Exp Mol Pathol 52:291–299, 1990PubMedGoogle Scholar
  54. 54.
    Arvidson B, Arvidsson J, Johansson K: Mercury deposits in neurons of the trigeminal ganglia after insertion of dental amalgam in rats. BioMetals 7:261–263, 1994PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Vera D. M. Stejskal
    • 1
  • Margit Forsbeck
    • 2
  • Karin E. Cederbrant
    • 1
  • Ola Asteman
    • 1
  1. 1.Astra ABSafety Assessment85 SödertäljeSweden
  2. 2.SophiahemmetStockholmSweden

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