title: Oral therapy with proteolytic enzymes decreases excessive TGF-beta 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-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).
  
  
  CONCLUSIONS
  These results support the concept that OET is beneficial in diseases characterized in part by TGF-beta1 overproduction.
authors.affiliation: Institute of Cancer Research, University of Vienna, Austria. ldesser@hotmail.com
authors.forename: L
authors.initials: L
authors.lastname: Desser
authors.forename: D
authors.initials: D
authors.lastname: Holomanova
authors.forename: E
authors.initials: E
authors.lastname: Zavadova
authors.forename: K
authors.initials: K
authors.lastname: Pavelka
authors.forename: T
authors.initials: T
authors.lastname: Mohr
authors.forename: I
authors.initials: I
authors.lastname: Herbacek
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood; D001963:Bromelains / Q000008:administration & dosage / Q000494:pharmacology; D002918:Chymotrypsin / Q000008:administration & dosage / Q000494:pharmacology; D004338:Drug Combinations; D010450:Endopeptidases / Q000008:administration & dosage / Q000494:pharmacology*; D006562:Herpes Zoster / Q000097:blood; D006801:Humans; D010206:Papain / Q000008:administration & dosage / Q000494:pharmacology; D055728:Primary Myelofibrosis / Q000097:blood; D012431:Rutin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D014357:Trypsin / Q000008:administration & dosage / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D004338:Drug Combinations; C119937:Phlogenzym; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000511:alpha-Macroglobulins; D012431:Rutin; D001963:Bromelains; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D010206:Papain