4.4 Article Proceedings Paper

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

Journal

CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 47, Issue -, Pages S10-S15

Publisher

SPRINGER
DOI: 10.1007/s002800170003

Keywords

transforming growth factor-beta; alpha2 macroglobulin; proteolytic enzymes; rheumatoid arthritis; herpes zoster; osteomyelofibrosis

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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-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce 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), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta 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-beta in serum (r = 0.8021; P < 0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or patients with a normal level of TGF-beta. 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 < 0.05). Conclusion: These results support the concept that OET is beneficial in diseases characterized in part by TGF-1 overproduction.

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