title: Fluoride augments the mitogenic and antigenic response of human blood lymphocytes in vitro.
abstract: It has been shown that fluoride, the agent responsible for reduction of dental caries worldwide and a recognized proliferative agent, is an adjuvant when given intragastrically to rats. Furthermore, plasma fluoride levels increase in humans after various fluoride treatments. The studies presented here show that fluoride also has the ability to affect the cells of the human immune system. This was tested by measuring the effect of sodium fluoride (NaF) on cytokine production by human whole blood cells stimulated in vitro. These studies revealed that NaF augments the human lymphocyte response from human blood to a mitogen (phytohemagglutinin, PHA) or a specific antigen (morbilli antigen from infected cells, MorbAg). The cytokine interferon-gamma (IFN-gamma), released from activated T and/or NK cells, was significantly (p<0.01) increased when whole blood cells were simultaneously incubated with 0.62 mmol/l NaF and PHA compared to PHA alone. This tendency was also true for NaF and MorbAg. The lymphocyte activation marker interleukin-2 receptor (measured in soluble form) increased after simultaneous stimulation of the cells with PHA and 0.62 mmol/l NaF compared to stimulation with PHA only. However, 0.62 mmol/l NaF did not enhance interleukin-6 release, in blood mainly produced by monocytes. The ability to influence the IFN-gamma release during an immune response could be one of the primary means by which the fluoride ion influences the immune system.
authors.affiliation: Division of Dental Toxicology, Department of Basic Oral Sciences, Karolinska Institute, Huddinge, Sweden. Annika.Loftenius@ofa.ki.se
authors.forename: A
authors.initials: A
authors.lastname: Loftenius
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: J
authors.initials: J
authors.lastname: Butler
authors.forename: J
authors.initials: J
authors.lastname: Ekstrand
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005459:Fluorides / Q000097:blood; D005460:Fluorides, Topical / Q000494:pharmacology*; D006389:Hemagglutinins, Viral / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D018375:Neutrophil Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012969:Sodium Fluoride / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D005460:Fluorides, Topical; D006389:Hemagglutinins, Viral; D015850:Interleukin-6; D008934:Mitogens; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D012969:Sodium Fluoride; D004247:DNA; D005459:Fluorides