Ability of recombinant human TNF binding protein-1 (r-hTBP-1) to inhibit the development of experimentally-induced endometriosis in rats.
The aim of this study was to assess whether r-hTBP-1 (recombinant human tumor necrosis factor binding protein-1), the soluble form of tumor necrosis factor-alpha (TNF) receptor type 1 might be effective in counteracting the proliferation of ectopic endometrium using an in vivo experimental model of endometriosis. The in vivo model involved transplanting a square fragment of autologus uterine tissue onto the inner surface of the abdominal wall in rats. r-hTBP-1 was administered for 1 week at 10 mg/kg, s.c. divided into two daily injections. The gonadotropin-releasing hormone antagonist antide was used for reference and given at the dose of 2 mg/kg, s.c. every 3 days for 1 week. The animals were killed 2 and 9 days after the last treatment and the size of endometriotic implants measured. Blood samples and spleens were also taken for assessment of estradiol-17beta levels and natural killer (NK) activity in vitro against murine YAC cells, respectively. The results of this study indicate that r-hTBP-1 is effective in reducing the size of the endometriotic-like foci mainly at the later sacrifice time-point when they were significantly decreased by 64% as compared to control animals. As expected, antide induces an almost complete and statistically significant remission both at the 2-day (94%) and the 9-day (88%); sacrifice time-point. Histological examination indicates that, compared to controls, r-hTBP-1 induces a slightly increased degeneration of the stromal tissues of the implants at both examination times and, limitedly to the earlier observation time, of the mucosal epithelium. No differences in the spleen cell NK activity were observed at either sacrifice time-points in any treatment group. Estradiol-17beta concentrations are significantly decreased in the antide-treated groups only at 9 days while no statistically significant changes are found in the animals receiving r-hTBP-1. The results of this study carried out in a rat experimental model of endometriosis provide evidence of the potential effectiveness of r-hTBP-1 in this pathological condition and support the role of TNF in its development.
D'Antonio
M
M
IRCS, Istituto di Ricerca C. Serono SpA, Via di Valle Caia 22, I-00040 Ardea, Rome, Italy. mauro.d'antonio.it_trn02@serono.com
Martelli
F
F
Peano
S
S
Papoian
R
R
Borrelli
F
F
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000627:therapeutic use*; D016466:CHO Cells; D006224:Cricetinae; D004195:Disease Models, Animal; D004715:Endometriosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004717:Endometrium / Q000276:immunology / Q000473:pathology; D004958:Estradiol / Q000097:blood; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000627:therapeutic use*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D015703:Antigens, CD; D006727:Hormone Antagonists; D009842:Oligopeptides; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; C057022:iturelix