Metal-specific lymphocyte reactivity is downregulated after dental metal replacement.

OBJECTIVES: This study was done to evaluate the results and clinical relevance of an optimized lymphocyte proliferation test, MELISA, for metal-induced inflammation in patients with CFS-like symptoms. The treatment of patients consisted of the replacement of incompatible dental materials (RID) together with supportive anti-oxidant therapy. DESIGN OF THE STUDY: 513 patients were tested by MELISA at the beginning of the study. Out of this group, 248 patients were available for follow-up MELISA after RID. METHODS: In MELISA, lymphocytes are isolated from the blood and cultivated with different metal salts in tissue culture medium containing 10% inactivated human AB+ serum or autologous serum. After 5 days, the presence of metal-reactive lymphocytes are measured by isotope labelling of newly formed DNA in growing lymphoblasts and evaluated by calculating the Stimulation Index. RESULTS: Nickel was the most common sensitizer, followed by inorganic mercury, thimerosal, lead, cadmium, palladium and gold. After RID treatment, a decrease of metal-specific lymphocyte responses in patients who reacted to metals at the beginning of the study could be observed. The cultivation of lymphocytes in autologous and homologous serum did not significantly affect the results. Simultaneous, the health status of patients improved as well. CONCLUSIONS: Replacement of incompatible dental materials resulted in down-regulation of metal-induced lymphocyte sensitivity in vitro, as well as in the improvement of health status of majority of patients with unspecific CFS-like symptoms.

Selenium protection against mercury-induced apoptosis and growth inhibition in cultured K-562 cells.

Selenium and mercuric chloride (MC) interactions regarding effects on cell growth and cell death have been studied. Human K-562 cells were pretreated or simultaneously treated with either selenite (5 or 50 microM) or selenomethionine (10 or 50 microM) and with MC (35 or 50 microM). The 35-microM MC treatments resulted in a clear inhibition of cell growth with no obvious difference between mercury-treated and mercury-selenium-treated cells. Furthermore, the apoptotic frequency was similar at all observations for all selenium treatments with 35 microM MC. In the simultaneously treated selenite and 50- microM MC combinations, a selenite-dependent protection was shown both by increased cell growth and by lower apoptotic frequency at 48 and 96 h of exposure. Both treatments with selenomethionine showed protection observed as an increased cell growth at 48 and 96 h and as decreased apoptotic frequency at 96 h of exposure.

Indications of selenium protection against cadmium toxicity in cultured K-562 cells.

The interaction between selenium and cadmium was studied in relation to cellular uptake and expressions of selenium-cadmium interaction. Human K-562 cells were pre-treated or simultaneously treated with (5 or 50 microM) selenite or (10 or 50 microM) selenomethionine and with (60 or 75 microM) cadmium nitrate. Cells pre or simultaneously treated with selenite revealed increased cadmium concentration with increased doses of selenite, particularly pronounced in the simultaneous treatments. In both treatments, selenium protection was observed during the exposure period, but not during the growth period. In cells simultaneously treated with selenomethionine and 60-microM cadmium, an increase in cadmium concentration was observed after increased selenium dose. In addition, it was found that simultaneous selenomethionine treatment with 60-microM cadmium resulted in selenium protection during the exposure period, although protection was not observed during the growth period.

Metal-specific lymphocytes: biomarkers of sensitivity in man.

Many patients attribute their health problems to amalgam and other dental metals. In genetically susceptible indviduals, mercury and gold may function as haptens and elicit allergic and autoimmune reactions. The frequency of metal-induced lymphocyte responses was examined in 3,162 patients in three European laboratories using MELISA(R), an optimized lymphocyte proliferation test. The patients suffered from local and systemic symptoms attributed to dental restorations. The effect of dental metal removal was studied in 111 patients with metal hypersensitivity and symptoms resembling Chronic Fatigue Syndrome (CFS). After consultation with a dentist the patients decided to replace their metal restorations with non-metallic materials. The changes in health and in vitro lymphocyte reactivity were studied by inquiries and follow-up MELISA(R). Lymphocyte reactivity was also analyzed in 116 healthy subjects with no complaints of metal allergy. A significant number of patients had metal-specific lymphocytes in the blood. Nickel was the most common sensitizer, followed by inorganic mercury, gold, phenylmercury, cadmium and palladium. As compared to lymphocyte responses in healthy subjects, the CFS group had significantly increased responses to several metals, especially to inorganic mercury, phenylmercury and gold. Following dental metal removal, 83 patients (76%) reported long-term health improvement. Twenty-four patients (22%) reported unchanged health and two (2%) reported worsening of symptoms. Following dental metal replacement, the lymphocyte reactivity to metals decreased as well. We propose that an inflammatory process induced by metals may modulate the hypothalamic-pituitary-adrenal axis (HPA axis) and trigger multiple non-specific symptoms characterizing CFS and other chronic conditions like myalgic encephalitis (ME) and multiple chemical sensitivity (MCS).