Combined nasal administration of encephalitogenic myelin basic protein peptide 68-86 and IL-10 suppressed incipient experimental allergic encephalomyelitis in Lewis rats

Mucosal administration of low doses of myelin basic protein (MBP) peptide 6 8-86 (MBP 68-86) or anti-inflammatory cytokine IL-10 effectively prevented experimental allergic encephalomyelitis (EAE), but failed to suppress the d isease if given after 7 days postimmunization (p.i.), i.e., after T cell pr iming had occurred. We anticipated that combined administration of autoanti gen and IL-10 can treat incipient EAE, Lewis rats with EAE actively induced with MBP 68-86 and complete Freund's adjuvant received 120 mu g MBP 68-86 + 200 ng IL-10 per rat per day from day 7 p.i. and for 5 consecutive days. These rats showed later onset, lower clinical scores, less body weight loss , and shorter duration of EAE than rats receiving MBP 68-86 or IL-10 only o r PBS, EAE amelioration was associated with decreased infiltration of ED1() macrophages and CD4(+) T cells within the central nervous system and with decreased proliferative responses of lymph node cells, indicating that com bined administration of MBP 68-86 and IL-10 induced immune hyporesponsivene ss. IFN-gamma secretion as well as IFN-gamma, TNF-alpha, IL-4, and IL-10 mR NA expression by lymph node MNC was down-regulated in the treated rats. Imm une hyporesponsiveness, rather than immune deviation or regulatory mechanis ms, seems to be responsible for the protection of EAE after autoantigen + I L-10 administration by the nasal route, (C) 2000 Academic Press.