Prevention of murine EAE by oral hydrolytic enzyme treatment.
Clinical trials that test the efficacy of Phlogenzym (consisting of the hydrolytic enzymes bromelain and trypsin and the anti-oxidant rutosid) as a treatment for T cell-mediated autoimmune diseases including multiple sclerosis (MS), type 1 diabetes and rheumatoid arthritis are presently ongoing. We tested the effects of Phlogenzym treatment in the murine model for MS, experimental allergic encephalomyelitis (EAE), a disease induced in SJL mice by immunization with proteolipid protein (PLP) peptide 139-151. Oral administration of Phlogenzym resulted in complete protection from EAE. In Phlogenzym-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 higher peptide concentrations to become activated. Additionally, the T cell response 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) were cleaved by Phlogenzym, while CD3 and MHC class II molecules (which are involved in the recognition of antigens by T cells) and LFA-1 were unaffected. These data show the efficacy of oral Phlogenzym treatment in an animal model of T cell-mediated autoimmune disease and suggest that the protective effect might be the result of an increase in the activation threshold of the autoreactive T lymphocytes brought about by the cleavage of accessory molecules involved in the interaction of T cells and antigen presenting cells.
Targoni
O S
OS
Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, 44106, USA.
Tary-Lehmann
M
M
Lehmann
P V
PV
D000284:Administration, Oral; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001963:Bromelains / Q000627:therapeutic use*; D004338:Drug Combinations; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy*; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012431:Rutin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014357:Trypsin / Q000627:therapeutic use*
D001324:Autoantigens; D004338:Drug Combinations; D015848:Interleukin-5; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C119937:Phlogenzym; C435023:myelin proteolipid protein (139-151); D015847:Interleukin-4; D012431:Rutin; D007371:Interferon-gamma; D001963:Bromelains; D014357:Trypsin