Autoimmune thyroid disease induced by thyroglobulin and lipopolysaccharide is inhibited by soluble TNF receptor type I.
Experimental autoimmune thyroiditis (EAT) is inducible in mice by immunization with thyroglobulin and adjuvant. Previous studies have shown that EAT is an autoimmune Th1-mediated disease but its characteristics differ with the adjuvant. Granulomatous lesions with marked follicular disruption develop following administration of thyroglobulin (Tg) and complete Freund's adjuvant (CFA) whereas when lipopolysaccharide (LPS) is used as the adjuvant only focal infiltrates of mononuclear cells are observed. The pro-inflammatory cytokine, TNF-alpha, is associated with Th1 autoimmune-mediated conditions. Cytokine antagonists have been used as potential therapeutic agents in several experimental autoimmune models. Soluble cytokine receptors belong to this category and may naturally be shed from cell membranes to inhibit cytokine activity. We show that the administration of the soluble TNF receptor type I (sTNFR I) in the induction of EAT has very different effects on the two models of induced autoimmune thyroiditis. sTNFR I treatment inhibits the induction of EAT only when mouse Tg is given with LPS not with CFA, suggesting an important difference in the pathogenic processes.
Zaccone
Paola
P
Department of Pathology, Immunology Division, Cambridge University, Cambridge, GB.
Fehérvári
Zoltán
Z
Blanchard
Lucy
L
Nicoletti
Ferdinando
F
Edwards
Carl K
CK
Cooke
Anne
A
D000276:Adjuvants, Immunologic; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D004334:Drug Administration Schedule; D005260:Female; D005620:Freund's Adjuvant; D007114:Immunization; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D023421:Models, Animal; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012995:Solubility; D018417:Th1 Cells / Q000276:immunology; D013954:Thyroglobulin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D013967:Thyroiditis, Autoimmune / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D005620:Freund's Adjuvant; D013954:Thyroglobulin