Linomide activates the adrenocortical axis in the rat: inhibition of experimental autoimmune encephalomyelitis by linomide is not related to the increase of corticosterone.
Linomide is a synthetic compound that affects various immunological functions and inhibits experimental autoimmune encephalomyelitis (EAE). In the present study we evaluated the effect of linomide on the HPA axis functions under basal and stress-induced conditions and examined whether the effect of linomide on the HPA axis is involved in linomide-induced amelioration of EAE in rats. Linomide caused a significant increase of serum ACTH and corticosterone (CS). The adrenocortical response to various stress modalities as well as the negative feedback exerted 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 inhibited by linomide treatment. These results suggest that the increased CS levels induced by linomide are responsible for the decrease in thymus weight but do not play a role in the therapeutic effect of this drug in EAE.
Weidenfeld
J
J
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Karussis
D
D
Abramsky
O
O
Lehmann
D
D
Arbell
I
I
Ovadia
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000302:Adrenal Cortex / Q000187:drug effects*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D005246:Feedback / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006912:Hydroxyquinolines / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013312:Stress, Physiological / Q000097:blood; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects
D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D006912:Hydroxyquinolines; C045282:roquinimex; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone