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

Desser L., Holomanova D.¹, Zavadova E. ², Pavelka K. ³, Mohr T., Herbacek I.

Institute of Cancer Research, University of Vienna,
¹Institute of Hematology and Transfusion Medicine, University of Bratislava, Bratislava, Slovak Republic
²Dept. of Immunology, St. Elisabeth Hospital, Prague, Czech Republic
³Institute of Rheumatology, Prague, Czech Republic

Work presented at ECCO 10, The European Cancer Conference, Vienna, 12-16 September 1999, and at 91st Meeting American Association of Cancer Research, San Francisco, 1-5 April 2000
Cancer Chemother Pharmacol (2001): 47 (Suppl), 10-15

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-b (TGF- b) production. It has been demonstrated that proteolytic enzymes reduce TGF- b levels in serum by converting the protease inhibitor a2 macroglobulin (a2M) from the "slow" form into the "fast" form, whereby the "fast" form binds and inactivates TGF- b irreversibly. In this study we have investigated the effect of OET on the concentration of TGF- b 1 in serum of patients with rheumatoid arthritis (RA) (n = 87), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 31). Seventy-eight healthy volunteers served as controls. TGF- b 1 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- b 1 in serum (r = 0.8021; -P<0.0001). Treatment with OET had no significant effect on TGF- b 1 concentration in healthy volunteers or patients with a normal level of TGF- b 1. In patients with elevated TGF- b 1 concentration (>50ng/ml serum), OET reduced TGF- b 1 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- b 1 overproduction.
Key words: Transforming growth factor-beta • Alpha 2 macroglobulin • Proteolytic enzymes • Rheumatoid arthritis • Herpes zoster • Osteomyelofibrosis