Recombinant Human TNFRSF1A (r-hTBP1) Inhibits the Development of Endometriosis in Baboons: A Prospective, Randomized, Placebo- and Drug-Controlled Study1

Thomas D’Hooghe, Thomas M D'Hooghe, Thomas D'Hooghe, Noreen P Nugent, Silvio Cuneo, Daniel C Chai, Daniel Chai, Frank Deer, Sophie Debrock, Cleophas Kyama, Cleophas M Kyama, Attila Mihalyi, Jason M Mwenda
Biology of reproduction · 2005 · vol. 74(1) , pp. 131–136 · doi:10.1095/biolreprod.105.043349 · PMID:16177224 · W2126781562
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Recombinant human TNFRSF1A (r-hTBP1) treatment reduced the development and severity of endometriosis lesions and adhesions in baboons, without causing hypoestrogenic effects.

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Abstract

Endometriosis is associated with chronic inflammation, including an increased macrophage activity with increased secretion of cytokines, such as tumor necrosis factor (TNF) or TNF superfamily member 2, previously known as TNFalpha. In the present study, we tested the hypothesis that recombinant human TNFRSF1A (r-hTBP1) can inhibit the development of endometriotic lesions in the baboon, an established model for the study of endometriosis. Endometriosis was induced using intrapelvic injection of menstrual endometrium in 20 baboons with a normal pelvis. In the first part of the study, 14 baboons were randomly assigned to subcutaneous treatment with r-hTBP1, placebo, or GnRH antagonist (positive control). In the second part of the study, menstrual endometrium from 6 baboons was randomly incubated with either PBS or r-hTBP1 before intrapelvic seeding. Video laparoscopy was performed 25 days later to document the number, surface area, and estimated volume of endometriotic lesions and adhesions; to calculate the revised American Fertility Society (rAFS) score and stage; and to confirm the histological presence of endometriosis. In the first part, baboons treated with r-hTBP1 or with Antide (Bachem) had a lower endometriosis rAFS score, a lower surface area and estimated volume of peritoneal endometriotic lesions, and a lower histological confirmation rate compared with controls. Because of less adnexal and cul-de-sac adhesions, the number of baboons with endometriosis of stage II, III, or IV was lower among baboons treated with r-hTBP1 or Antide than among controls. In the second part, the surface area of endometriotic lesions was lower, and less severe endometriosis was observed in r-hTBP1-treated baboons. No hypoestrogenic effects were observed in baboons treated with r-hTBP1. In conclusion, r-hTBP1 can effectively inhibit the development of endometriosis without hypoestrogenic effects in baboons.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Receptors, Tumor Necrosis Factor, Type I Animals Disease Models, Animal Endometriosis Endometriosis Female Gonadal Steroid Hormones Gonadal Steroid Hormones Menstrual Cycle Menstrual Cycle Menstrual Cycle Papio anubis Perineum Perineum Prospective Studies Receptors, Tumor Necrosis Factor, Type I

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