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

Cancer Chemother Pharmacol. 2001 Jul;47 Suppl:S10-5. doi: 10.1007/s002800170003.

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-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) 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-beta1 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-beta1 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-beta1 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-beta1. 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-beta1 overproduction.

MeSH terms

  • Administration, Oral
  • Adult
  • Arthritis, Rheumatoid / blood
  • Bromelains / administration & dosage
  • Bromelains / pharmacology
  • Chymotrypsin / administration & dosage
  • Chymotrypsin / pharmacology
  • Drug Combinations
  • Endopeptidases / administration & dosage
  • Endopeptidases / pharmacology*
  • Herpes Zoster / blood
  • Humans
  • Papain / administration & dosage
  • Papain / pharmacology
  • Primary Myelofibrosis / blood
  • Rutin / administration & dosage
  • Rutin / analogs & derivatives*
  • Rutin / pharmacology
  • Transforming Growth Factor beta / blood*
  • Transforming Growth Factor beta1
  • Trypsin / administration & dosage
  • Trypsin / pharmacology
  • alpha-Macroglobulins / metabolism

Substances

  • Drug Combinations
  • Phlogenzym
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • alpha-Macroglobulins
  • Rutin
  • Bromelains
  • Endopeptidases
  • Chymotrypsin
  • Trypsin
  • Papain