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.