Isotype-restricted hyperimmunity in a murine model of the toxic oil syndrome.
The toxic oil syndrome is characterized by IgE elevation and eosinophilia, as well as scleroderma-like skin manifestations and other symptoms of autoimmune disease. Fatty acid anilides, found in large amounts in adulterated cooking oil, were suspected to be the etiologic agent in this disease. The capacity of oleic acid anilide to induce features of autoimmunity in vivo was investigated. B10.S mice were continuously treated i.p. with oleic acid anilide for 6 wk by using osmotic pumps. A significant increase in IgE and IgM serum levels was observed after 1 to 3 wk; subsequently five of six mice developed IgG1 levels 3.5- to 10-fold higher than the controls. Anilide-treated mice developed splenomegaly with a 2.1- and a 3.5-fold increase in IgM- and IgG-bearing splenocytes, respectively, and a 5.6- and 29-fold elevation in functional IgM- and IgG-secreting cells, respectively. Increased serum levels of predominantly IgM antibodies to histone, denatured DNA, and DNP as well as rheumatoid factor were detected. In vivo expression in the spleen of 10 cytokine genes was also examined, and mRNA encoding IL-1 beta and IL-6 were significantly elevated in splenocytes of anilide-treated mice. The enhanced Ig production suggests that anilide induced a cytokine-mediated polyclonal activation of B cells. Elicitation of IgM antibodies to denatured forms of autoantigens indicates that anilide treatment partially broke autoimmune tolerance in these mice. Anilide-treated mice may be a useful animal model for further exploring the mechanism and pathogenesis of systemic autoimmunity in the toxic oil syndrome.
Bell
S A
SA
W.M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, La Jolla, CA.
Hobbs
M V
MV
Rubin
R L
RL
D000813:Anilides / Q000276:immunology* / Q000633:toxicity; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology*; D001937:Brassica; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated; D015870:Gene Expression; D006657:Histones / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D009829:Oleic Acids / Q000276:immunology* / Q000633:toxicity; D010938:Plant Oils / Q000506:poisoning*; D012333:RNA, Messenger / Q000235:genetics; D000074262:Rapeseed Oil; D012217:Rheumatoid Factor / Q000276:immunology; D013577:Syndrome
D000813:Anilides; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016207:Cytokines; D005229:Fatty Acids, Monounsaturated; D006657:Histones; D007132:Immunoglobulin Isotypes; D009829:Oleic Acids; D010938:Plant Oils; D012333:RNA, Messenger; D000074262:Rapeseed Oil; C038731:oleoylanilide; D012217:Rheumatoid Factor