Intranasal administration of recombinant mouse interleukin-12 increases inflammation and demyelination in chronic experimental autoimmune neuritis inLewis rats

To examine whether interleukin (IL)-12 modulates ongoing chronic experiment al autoimmune neuritis (EAN), we evaluated the effects of recombinant mouse IL-12 (rmIL-12) in Lewis rats with chronic EAN, induced by immunization wi th P0 peptide (180-199)plus complete Freund's adjuvant. Rats were treated i ntranasally with either 0.1 or 1 mu g/rat/day rmIL-12 for 6 days from the o nset of clinical chronic EAN, on days 5-10 postimmunization (p.i.). Only hi gh-dose rmIL-12 exacerbated chronic EAN. This clinical effect was associate d with higher numbers of inflammatory cells and more severe demyelination i n sciatic nerve sections on days 15 and 80 p.i. compared with low-dose rmIL -12-treated rats and phosphate-buffered saline (PBS)-treated control rats. High-dose rmIL-12 increased significantly the lymph node mononuclear cell p roliferation in response to P0 peptide 180-199 and IFN-gamma production in the sciatic nerves. These data indicate that intranasally administered IL-1 2 acts as a proinflammatory cytokine in chronic EAN. Effective inhibition o f IL-12 in vivo could be considered for therapeutic use in chronic inflamma tory demyelinating polyradiculoneuropathy.