Involvement of nuclear factor-kappa B in a murine model for the acute formof autoimmune-like toxic oil syndrome

The toxic oil syndrome (TOS) represents an exogenously induced autoimmune d isease with acute or chronic symptoms similar to systemic lupus erythematos us or scleroderma. When genetically different mouse strains were exposed to oleic acid anilide (OAA), it was possible to mimic the different syndrome manifestations. The aim of the present study was to examine the role of NF- kappa B/Rel transcription factors in the development of the severe acute wa sting disease observed in A/J mice. Within a week of OAA exposure, the A/J, but not B10.S strain, displayed weight loss, cachexia, apathy, reduced act ivity, and breathing difficulties. In affected A/J mice we observed a marke d increase in NF-kappa B activation (p50/p65 dimers) both in splenic T cell s and peritoneal macrophages as well as in tissue from aorta and gut. Incub ation of splenocytes with OAA in vitro induced a dose-dependent removal of I kappa B-alpha, accompanied by NF-kappa B activation, whereas Sp-1 binding was not affected. Furthermore, we demonstrated the increased expression of the two NF-kappa B target genes IL-6 and IL-1 beta in OAA-exposed mice and a transient OAA-induced accumulation of TNF alpha in vitro. This is the fi rst report which implicates NF-kappa B/Rel in acute forms of chemically ind uced autoimmune-like disease and may serve as a paradigm for the involvemen t of this transcriptional system in acute processes associated with autoimm unity, suggesting possible avenues of therapeutic intervention. (C) 1999 Ac ademic Press.