CUTTING EDGE - ANTISENSE KNOCKDOWN OF INDUCIBLE NITRIC-OXIDE SYNTHASEINHIBITS INDUCTION OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN SJL J MICE/

We used an antisense oligodeoxynucleotide (ODN) complementary to induc ible nitric oxide synthase (iNOS) to inhibit experimental autoimmune e ncephalomyelitis (EAE) in female SJL/J mice, an animal model for multi ple sclerosis, The antisense ODN was administered intraventricularly t o mice daily for 10 days beginning at the time of adoptive transfer of myelin basic protein-specific T lymphocytes. The antisense ODN treatm ent significantly reduced the clinical score of EAE and blocked iNOS m RNA and protein synthesis, as well as iNOS enzyme activity within the central nervous system, The levels of nitric oxide and cyclic guanosin e monophosphate were also significantly reduced by the antisense ODN t reatment, Neither sense nor random ODN affected clinical EAE or iNOS e xpression, Moreover, the protein and enzyme activity level of constitu tive neuronal nitric oxide synthase was not affected by the antisense ODN, Thus, we have shown that the iNOS antisense ODN specifically bloc ked iNOS expression and ameliorated the induction of EAE.