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.
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.
Hansson
Monika
M
Department of Immunology, the Wenner-Gren Institute, Arrhenius Laboratories for the Natural Sciences, Stockholm University, Stockholm, Sweden.
Djerbi
Mounira
M
Rabbani
Hodjattallah
H
Mellstedt
Håkan
H
Gharibdoost
Farhad
F
Hassan
Moustapha
M
Depierre
Joseph W
JW
Abedi-Valugerdi
Manuchehr
M
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
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
Scand J Immunol. 2002 May;55(5):493-502
11975761
Clin Exp Immunol. 2001 Oct;126(1):157-64
11678913
Springer Semin Immunopathol. 2003 Aug;25(1):3-18
12904888
Scand J Immunol. 2004 May;59(5):469-77
15140057
Eur J Immunol. 1976 Aug;6(8):588-90
789096
Nature. 1980 Feb 14;283(5748):666-8
6153460
J Immunol. 1981 Feb;126(2):699-792
7005342
Clin Exp Immunol. 1984 Nov;58(2):300-6
6333944
J Clin Lab Immunol. 1989 Mar;28(3):143-50
2786961
Br J Exp Pathol. 1989 Jun;70(3):227-36
2527550
J Immunol. 1991 Dec 15;147(12):4185-91
1753095
Clin Immunol Immunopathol. 1992 Nov;65(2):98-109
1395135
Immunopharmacology. 1994 Nov-Dec;28(3):201-8
7852051
Immunol Today. 1995 Feb;16(2):90-8
7888073
Immunol Today. 1995 Mar;16(3):150-9
7718089
Curr Opin Immunol. 1995 Dec;7(6):831-8
8679128
Eur J Immunol. 1996 Jul;26(7):1519-26
8766555
J Autoimmun. 1996 Apr;9(2):139-49
8738957
J Autoimmun. 1995 Dec;8(6):809-23
8824708
Genome Res. 1996 Oct;6(10):986-94
8908518
J Autoimmun. 1997 Aug;10(4):347-55
9237798
Life Sci. 1997;61(19):1861-78
9364191
Int J Occup Med Environ Health. 1997;10(3):247-58
9524402
Clin Exp Immunol. 1998 Mar;111(3):521-6
9528892
J Immunol. 1998 Jul 1;161(1):234-40
9647229
Immunol Res. 1999;20(1):67-78
10467984
Food Chem Toxicol. 1999 Jun;37(6):627-37
10478831
Environ Health Perspect. 1999 Oct;107 Suppl 5:807-10
10502547
Int Immunol. 2000 Oct;12(10):1425-30
11007760
Environ Health Perspect. 2001 Jan;109(1):27-33
11171521
J Autoimmun. 2001 May;16(3):319-26
11334498
J Toxicol Environ Health B Crit Rev. 2001 Apr-Jun;4(2):161-205
11341073
Scand J Immunol. 2001 Jul-Aug;54(1-2):190-7
11439166
J Exp Med. 2001 Jul 16;194(2):165-72
11457891
J Immunol. 2001 Aug 15;167(4):2396-403
11490030
Nat Immunol. 2001 Sep;2(9):759-61
11526377
Clin Exp Immunol. 2001 Aug;125(2):202-10
11529910
Immunology. 2001 Aug;103(4):407-16
11529930
Environ Health Perspect. 2003 Aug;111(10):1273-7
12896845