Inhibition of experimental autoimmune neuritis by the immunomodulator linomide.
Experimental autoimmune neuritis (EAN) is an animal model that shares clinical, pathological and electrophysiological features with the human disease Guillain-Barre syndrome. The synthetic immunomodulatory substance linomide has been successfully used to prevent the development of several experimental autoimmune models in laboratory animals and has been proved to be beneficial in modulating the course of multiple sclerosis in humans. In the present study we demonstrate that oral administration of linomide prevents the development of clinical and histopathological signs of EAN in Lewis rats, inoculated with the P2 (60-70) synthetic peptide. The immunomodulatory effect of linomide on this experimental model of disease was associated with marked apoptosis of lymphocytes in thymus and spleen early after starting the treatment. Furthermore, a downregulation of the endothelial expression of the adhesion molecules ICAM-1 at the target site and LFA-1 on lymphocytes could also contribute to the absence of inflammatory cells in the neuraxis.
Karpati
T
T
Department of Neurology, Hadassah University Hospital, Hebrew University Hadassah, Medical School, Jerusalem, Israel.
Karussis
D
D
Abramsky
O
O
Mizrahi-Koll
R
R
Arbell
I
I
Ovadia
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D005260:Female; D006912:Hydroxyquinolines / Q000494:pharmacology*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D018996:Myelin P2 Protein / Q000138:chemical synthesis / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; D016169:Lymphocyte Function-Associated Antigen-1; D018996:Myelin P2 Protein; D018799:Intercellular Adhesion Molecule-1; C045282:roquinimex