therapy with proteolytic enzymes decreases excessive TGF-beta levels in human
L, Holomanova D, Zavadova E, Pavelka K, Mohr T, Herbacek I
of Cancer Research, University of Vienna, Austria.
with oral proteolytic enzymes (OET) with combination drug products containing
papain, bromelain, trypsin, and chymotrypsin has been shown to be beneficial in
clinical settings such as radiotherapy-induced fibrosis, bleomycin
pneumotoxicity and immunosuppression in cancer, all of which are nowadays known
to be accompanied by excessive transforming growth factor-beta (TGF-beta)
It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in
serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) from
the "slow" form into the "fast" form, whereby the
"fast" form binds and inactivates TGF-beta irreversibly.
In this study we have investigated the effect of OET on the concentration of
TGF-beta1 in serum of patients with rheumatoid arthritis (RA) (n = 38),
osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7).
Seventy-eight healthy volunteers served as controls.
TGF-beta1 levels in serum were assessed by enzyme-linked immunosorbent assay
We have demonstrated that in healthy volunteers and in patients there exists a
correlation between active and latent TGF-beta1 in serum (r=0.8021;
Treatment with OET had no significant effect on TGF-beta1 concentration in
healthy volunteers or patients with a normal level of TGF-beta1.
In patients with elevated TGF-beta1 concentration (> 50 ng/ml serum), OET
reduced TGF-beta1 in RA (P < 0.005), in OMF (P < 0.05) and in HZ (P <
These results support the concept that OET is beneficial in diseases
characterized in part by TGF-beta1 overproduction.
PMID: 11561866 [PubMed - indexed for MEDLINE]