Prevention of murine EAE by oral hydrolytic enzyme treatment

Clinical trials that test the efficacy of Phlogenzym (consisting of the hyd rolytic enzymes bromelain and trypsin and the anti-oxidant rutosid) as a tr eatment for T cell-mediated autoimmune diseases including multiple sclerosi s (MS), type 1 diabetes and rheumatoid arthritis are presently ongoing. We tested the effects of Phlogenzym treatment in the murine model for MS, expe rimental allergic encephalomyelitis (EAE), a disease induced in SJL. mice b y immunization with proteolipid protein (PLP) peptide 139-151. Oral adminis tration of Phlogenzym resulted in complete protection from EAE. In Phlogenz ym-treated mice, the dose response curve of the PLP:139-151-specific T cell response was shifted to the right, that is, the primed T cells required hi gher peptide concentrations to become activated. Additionally, the T cell r esponse to this peptide was shifted towards the T helper 2 cytokine profile . Both effects are consistent with an increased T cell activation threshold . In support of this interpretation, we found that the accessory molecules CD4, CD44, and B7-1 (all of which are involved in T cell co-stimulation) we re cleaved by Phlogenzym, while CD3 and MHC class II molecules (which are i nvolved in the recognition of antigens by T cells) and LFA-I were unaffecte d. These data show the efficacy of oral Phlogenzym treatment in an animal m odel of T cell-mediated autoimmune disease and suggest that the protective effect might be the result of an increase in the activation threshold of th e autoreactive T lymphocytes brought about by the cleavage of accessory mol ecules involved in the interaction of T cells and antigen presenting cells. (C) 1999 Academic Press.