Abstract
Therapy 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-β (TGF-β) production. It has been demonstrated that proteolytic enzymes reduce TGF-β levels in serum by converting the protease inhibitor α2 macroglobulin (α2M) from the “slow” form into the “fast” form, whereby the “fast” form binds and inactivates TGF-β irreversibly. In this study we have investigated the effect of OET on the concentration of TGF-β1 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-β1 levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and latent TGF-β1 in serum (r=0.8021; P<0.0001). Treatment with OET had no significant effect on TGF-β1 concentration in healthy volunteers or patients with a normal level of TGF-β1. In patients with elevated TGF-β1 concentration (>50 ng/ml serum), OET reduced TGF-β1 in RA (P<0.005), in OMF (P<0.05) and in HZ (P<0.05). Conclusion: These results support the concept that OET is beneficial in diseases characterized in part by TGF-β1 overproduction.
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Desser, L., Holomanova, D., Zavadova, E. et al. Oral therapy with proteolytic enzymes decreases excessive TGF-β levels in human blood. Cancer Chemother Pharmacol 47 (Suppl 1), S10–S15 (2001). https://doi.org/10.1007/s002800170003
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DOI: https://doi.org/10.1007/s002800170003