title: Exposure to mercuric chloride during the induction phase and after the onset of collagen-induced arthritis enhances immune/autoimmune responses and exacerbates the disease in DBA/1 mice.
abstract: In susceptible mice, mercuric chloride induces a systemic autoimmune response that is characterized by elevated serum levels of immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), production of anti-nucleolar antibodies (ANolAs) and the formation of renal IgG deposits. We have previously shown that mercury can also enhance immune/autoimmune responses in mouse strains genetically prone to develop spontaneous autoimmune disease. Here, we investigated whether mercury can enhance the severity of murine collagen-induced arthritis (CIA), an inducible (acquired) autoimmune disease that cannot be induced by mercury itself. While mercury administered prior to the induction phase of CIA exerted little, if any, influence, administration of mercury during the induction phase and following onset aggravated the symptoms of this disease and increased the serum levels of IgE and IgG2a antibodies directed against collagen type II (CII). Furthermore, while animals injected with mercury alone exhibited a significant decrease in the ratio of the levels of interferon-gamma (IFN-gamma) to interleukin-4 (IL-4) mRNA in their spleens, this ratio was increased in mice with CIA, with or without administration of mercury. Finally, the production of anti-nuclear antibodies, a hallmark of autoimmunity in response to mercury, was observed in all mice with CIA treated with this heavy metal. Our findings suggest that exposure to mercury during the development of CIA may influence immunological factors in such a way as to synergistically promote disease development.
authors.affiliation: Department of Immunology, the Wenner-Gren Institute, Arrhenius Laboratories for the Natural Sciences, Stockholm University, Stockholm, Sweden.
authors.forename: Monika
authors.initials: M
authors.lastname: Hansson
authors.forename: Mounira
authors.initials: M
authors.lastname: Djerbi
authors.forename: Hodjattallah
authors.initials: H
authors.lastname: Rabbani
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
authors.forename: Farhad
authors.initials: F
authors.lastname: Gharibdoost
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Depierre
authors.forename: Manuchehr
authors.initials: M
authors.lastname: Abedi-Valugerdi
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008627:Mercuric Chloride / Q000276:immunology / Q000633:toxicity*; D051379:Mice; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D024043:Collagen Type II; D007074:Immunoglobulin G; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D007371:Interferon-gamma
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