Prevention of Murine EAE by Oral Hydrolytic Enzyme Treatment
Targoni
O.S., Tary-Lehmann M. and Lehmann P.V. Prevention of Murine EAE by
Oral Hydrolytic Enzyme Treatment. Journal of Autoimmunity 1999, Vol.
12, pp. 191-198, PZ 14 (18-02-3)
Institute of Pathology, School of Medicine, Case Western Reserve
University, Cleveland, Ohio 44106, USA
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.
Key words: phlogenzym, enzyme therapy, EAE, accessory molecules, T
cell activation threshold