Autoimmunity travelled from the theoretical roots planted by Burnet with the clonal selection theory and the early finding of a mouse providing a test for the role of the thymus as a source of forbidden clones. This chapter briefly reviews early work with the NZB mouse and presents results of an analysis of associations between cytokines and physical and psychometric parameters in systemic lupus erythematosus (SLE) patients not medicated with antidepressants. Some cytokines, particularly IFN-gamma, relate significantly to physical symptoms and anxiety. We conclude with the speculation that anxiety is linked to innate immunity and more severe neuropsychiatric disease in SLE to adaptive immunity.

We observed a consistent sequence of activation changes in rat knee synovia following a single intravenous injection of sterile ferric citrate at a dosage sufficient to cause a transient saturation of transferrin. The initial alteration, appreciated 2 hours postinjection, consisted of an expansion in the lumen of synovial capillaries. At 8 hours, a thickening of the synovial lining and subsynovial tissue due to the hypervascularity and increased cellularity was noted, along with peaks in the mitotic activity of synovial cells (fourfold over baseline) and pinocytosis by endothelial cells. During the period of 8-24 hours, mature collagen appeared in the space between pericyte layers and between pericytes and endothelial cells, and 2-9-fold increases in ferritin + , W3/13 + , W3/25 + , Ox8 + , and 0x26 + mononuclear cells occurred. In contrast to the action on synovial

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