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

Therapy with oral proteolytic enzymes (OET) with combination drug products containing papain, bromelain, trypsin, and chymotrypsin has been shown to b e beneficial in clinical settings such as radiotherapy-induced fibrosis, bl eomycin pneumotoxicity and immunosuppression in cancer, all of which are no wadays known to be accompanied by excessive transforming growth factor-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes r educe TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha 2M) 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-beta in serum of patients with rheumatoid arthritis (RA) (n = 38), osteomyelofibro sis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy vol unteers served as controls. TGF-beta levels in serum were assessed by enzym e-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and la tent TGF-beta in serum (r = 0.8021; P < 0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or pati ents with a normal level of TGF-beta. In patients with elevated TGF-beta1 c oncentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P < 0.005), i n OMF (P < 0.05) and in HZ (P < 0.05). Conclusion: These results support th e concept that OET is beneficial in diseases characterized in part by TGF-< beta>1 overproduction.