The possible involvement of glucocorticoids in the development of genetically determined autoimmune pathology in NZB...

The total blood corticosterone concentration, the reactivity of the adrenal glands to exogenous adrenocorticotrophic hormone, and the binding capacity of corticosteroid-binding globulin (CBG), were determined in male NZB mice that spontaneously develop an autoimmune disease. The appearance of antibodies to endogenous erythrocytes was also monitored. This study was performed on animals of the following age groups: (1) 2-3-month-old animals prior to the appearance of autoantibodies; (2) 6-7-month-old animals in the period when the disease developed; and (3) 10-12-month-old animals, i.e. the period when the autoimmune disease developed. It was demonstrated that in the 10-12-month-old mice there was a sharp decrease in the total corticosterone level in the plasma (from 152 +/- 32 to about 20 micrograms l-1), and the reactivity of the adrenal glands to exogenous corticotrophin decreased (from 400% to 120%). However, the binding capacity of CBG increased with age which led to a decrease in the pool of active corticosterone in the blood. The increase in this capacity was especially pronounced in affected 10-12-month-old animals. (The number of binding sites increased from 0.64 +/- 0.05 to 0.8 +/- 0.03 microM and the values of the association constant for the binding of corticosterone to CBG increased from 0.29 +/- 0.05 to 0.91 +/- 0.07 microM-1). The combination of the above-mentioned changes suggests that there is a direct correlation between the decrease in the glucocorticoid background in the NZB mice and in the appearance of autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)