Oral therapy with proteolytic enzymes decreases excessive TGF-β levels in human blood

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.