Intratracheal administration to the lung enhances therapeutic benefit of an MBP peptide in the treatment of murine experimental autoimmune encephalomyelitis

The treatment of autoimmune diseases by targeted down-regulation of autoant igen-specific cells has been accomplished by the administration of high dos es of autoantigen. We performed direct comparisons between injection of mye lin basic protein peptide and administration by several nonparenteral route s to determine whether route impacted benefit in the treatment of murine al lergic encephalomyelitis, a model for multiple sclerosis. The range of effe ctive peptide doses spanned over 1000-fold, and route of delivery played a major role in determining optimal dose. The oral route of administration wa s the least effective, requiring at least 50- to 100-fold more antigen than subcutaneous injection, which in turn required at least 10-fold more antig en than delivery of peptide to the lung using an intratracheal instillation . Intratracheal delivery was also considerably more effective than inhalati on of peptide, and, unlike inhalation, resulted in obvious penetration of d elivered material deep into the lung. The increase in therapeutic efficacy did not appear to result from slower systemic delivery of antigen. Accumula tion of peptide on antigen presenting cells in the spleen and in the brain was less efficient using the intratracheal route of administration compared to subcutaneous injection, implicating a special role for the lung microen vironment in the induction of immune nonresponsiveness. (C) 2000 Academic P ress.