LINOMIDE ACTIVATES THE ADRENOCORTICAL AXIS IN THE RAT - INHIBITION OFEXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY LINOMIDE IS NOT RELATED TO THE INCREASE OF CORTICOSTERONE

Linomide is a synthetic compound that affects various immunological fu nctions and inhibits experimental autoimmune encephalomyelitis (EAE). In the present study we evaluated the effect of linomide on the HPA ax is functions under basal and stress-induced conditions and examined wh ether the effect of linomide on the HPA axis is involved in linomide-i nduced amelioration of EAE in rats. Linomide caused a significant incr ease of serum ACTH and corticosterone (CS). The adrenocortical respons e to various stress modalities as well as the negative feedback exerte d by glucocorticoids was not affected. The marked reduction of thymus weight following linomide treatment was abrogated in adrenalectomized rats. The induction of EAE in adrenalectomized rats was completely inh ibited by linomide treatment. These results suggest that the increased CS levels induced by linomide are responsible for the decrease in thy mus weight but do not play a role in the therapeutic effect of this dr ug in EAE. (C) 1997 Elsevier Science B.V.