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Hum. Reprod. Advance Access published online on March 3, 2006
Human Reproduction, 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
Received October 30, 2005
Revised January 13, 2006
Accepted January 20, 2006

Article

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 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
5 Department of Obstetrics and Gynaecology, Danderyds Hospital, Stockholm, Sweden
6 Institute of Primate Research, Nairobi, Kenya; Department of Obstetrics and Gynaecology, Leuven University Fertility Center, Leuven, Belgium

* To whom correspondence should be addressed.
T.M. D’Hooghe, E-mail: thomas.dhooghe{at}uz.kuleuven.ac.be


  Abstract

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 video-laparoscopy 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 endome-triosis, 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.

Keywords: anti-TNF/baboon/cytokines/endometriosis/randomized controlled study.
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