Enhancement of acute phase and inhibition of chronic phase of experimentalautoimmune neuritis in Lewis rats by intranasal administration of recombinant mouse interleukin 17: Potential immunoregulatory role

Experimental autoimmune neuritis (EAN) is a CD4(+) T-cell-mediated demyelin ating disease of the peripheral nervous system (PNS). We examined the effec t of recombinant mouse interleukin 17 (rmIL-17) on chronic EAN induced in L ewis rats by inoculation of P2 57-81 peptide in Freund's complete adjuvant. Animals were treated nasally for 6 days with either 0.1 or 0.9 I mu g/rat/ day rmIL-17 from the onset of neurological signs, i.e., days 9 to 14 postim munization (p.i.). Prolonged follow-up demonstrated a chronic course in con trol and rmIL-17-treated rats. Treated rats had more severe disease initial ly (days 18-36 p.i.) with a stronger enhancing effect observed with the hig her rmIL-l7 dose. At day 19 rmIL-17-treated rats showed increased infiltrat ion of inflammatory cells into the sciatic nerve, more severe demyelination , augmented proliferation of regional lymph node cells, and increased serum levels of tumor necrosis factor-alpha. After the initial phase of disease enhancement the IL-17-treated EAN rats improved gradually and ultimately re covered completely, whereas the control EAN rats remained affected until th e end of the observation (day 120 p.i.). The lower dose of rmIL-17 induced an earlier recovery from clinical deficits than the higher one. The results indicate that IL-17 plays an immunoregulatory role in chronic EAN which co uld have implications for immunomodulatory treatments of chronic autoimmune disease of the PNS. (C) 2000 Academic Press.