Tumour necrosis factor-alpha is a fundamental cytokine in autoimmune thyroid disease induced by thyroglobulin and lipopolysaccharide in interleukin-12 p40 deficient C57BL/6 mice.
Experimental autoimmune thyroiditis (EAT) is inducible in mice by immunization with mouse thyroglobulin (mTg) together with adjuvant, either lipopolysaccharide (LPS) or complete Freund's adjuvant (CFA). The severity of the disease is dependent on the mouse strain and on the adjuvant used. We have previously shown that interleukin (IL)-12 deficient C57BL/6 mice immunized with mTg and CFA develop a significantly less severe thyroid infiltration in comparison to wild type C57 BL/6 mice. This result indicated a pivotal role for IL-12 in the development of thyroiditis induced with CFA and mTg. In the present study we demonstrate that IL-12 deficiency does not impair EAT induction when LPS is used as adjuvant. We also demonstrate that peritoneal exudate cells from IL-12-deficient mice stimulated in vitro either with LPS or IL-18 secrete high levels of tumour necrosis factor (TNF). Together the results emphasize the difference between the use of CFA and LPS in the induction of EAT, the importance of TNF-alpha for the pathogenesis of LPS-induced EAT, and also show the capacity of IL-12-deficient mice to develop a competent response to LPS.
Zaccone
Paola
P
Department of Pathology, Immunology Division, Cambridge University, Cambridge, UK.
Fehérvári
Zoltán
Z
Cooke
Anne
A
D000276:Adjuvants, Immunologic; D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000172:deficiency* / Q000235:genetics; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D021122:Protein Subunits / Q000172:deficiency* / Q000235:genetics; D013954:Thyroglobulin; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000276:Adjuvants, Immunologic; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D008070:Lipopolysaccharides; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D005620:Freund's Adjuvant; D013954:Thyroglobulin