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Hum. Reprod. Advance Access originally published online on March 3, 2006
Human Reproduction 2006 21(7):1856-1862; doi:10.1093/humrep/del044
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© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon

H. Falconer 1 , J.M. Mwenda 2 , D.C. Chai 2 , C. Wagner 3 , X.Y. Song 3 , A. Mihalyi 4 , P. Simsa 4 , C. Kyama 4 , F.J. Cornillie 3 , A. Bergqvist 5 , G. Fried 1 and T.M. D’Hooghe 2 , 4 , 6

1 Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden 2 Institute of Primate Research, Nairobi, Kenya 3 Centocor Inc; Malvern, PA, USA 4 Department of Obstetrics and Gynaecology, Leuven University Fertility Center, Leuven, Belgium and 5 Department of Obstetrics and Gynaecology, Danderyds Hospital, Stockholm, Sweden.

6 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Leuven University Fertility Center, UZ Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium. E-mail: thomas.dhooghe{at}uz.kuleuven.ac.be

BACKGROUND: Inflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-{alpha}), are important in the pathogenesis of endometriosis. We assessed the efficacy of anti-TNF monoclonal antibody (mAb, c5N), known to prevent induced endometriosis in baboons, in reducing established endometriosis in baboons. METHODS: This prospective, randomized, blinded, controlled study was conducted in baboons at the Institute of Primate Research (IPR), Nairobi, Kenya. Endometriosis was induced in 18 adult female baboons (Papio anubis) with regular menstrual cycles and a normal pelvis; the extent of endometriosis was documented by videolaparoscopy 25 days later. The baboons were then randomly assigned to receive a single infusion of either placebo (n = 7, 5 ml/kg) or c5N (n = 11, 5 mg/kg). Follow-up laparoscopy was performed 25 days later to document any differences in the number, surface area and estimated volume of lesions between the two groups and between the first and the second laparoscopies in each group. Representative biopsies of at least one endometriotic lesion per baboon were obtained at the final laparoscopy. RESULTS: Significant reductions in total surface area, estimated total volume of endometriotic lesions and both number and surface area of red lesions were observed after treatment with c5N, but not after placebo treatment, when compared to the initial laparoscopy. Conversely, a significant increase in the number of typical and red lesions was observed after placebo treatment when compared to the initial laparoscopy. Neither c5N nor placebo treatment affected the menstrual cycle. CONCLUSION: In baboons with induced endometriosis, anti-TNF-mAb (c5N) treatment significantly reduced the extent of endometriosis, mainly due to reducing both the number and surface area of red lesions. These findings suggest that anti-TNF-mAb therapy may have therapeutic potential for active peritoneal endometriosis.

Key words: anti-TNF/baboon/cytokines/endometriosis/randomized controlled study


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