Prevention of ovarian hyperstimulation syndrome in a rat model: comparison of the efficacy of tocilizumab with that of ranibizumab, cabergoline, and a gonadotropin-releasing hormone antagonist

Abstract

The aim of the study is to investigate the effects of the interleukin-6 (IL-6) blocker tocilizumab in a hyperstimulated rat model and compare it with ranibizumab, a gonadotropin-releasing hormone antagonist (GnRHA), and cabergoline. Forty-seven rats were randomly divided into the following seven groups: Group 1: OHS; Group 2: OHS+ GnRHA; Group 3: OHS + ranibizumab; Group 4: OHS + cabergoline; Group 5: OHS + low-dose tocilizumab (TL); Group 6: OHS + high-dose tocilizumab (TH); Group 7: sham. Ovarian weight was significantly lower only in the ranibizumab group than in the OHS group. Estrogen levels were significantly lower in the GnRHA group than in the OHS and the treatment groups. Progesterone levels were significantly lower in the ranibizumab, cabergoline, and TL groups than in the OHS group. Among the treatment groups, corpus luteum counts were lower than in the OHS group. Corpus luteum counts were lowest in the tocilizumab groups. IL-6 intensity was lower in all treatment groups than in the OHS group. In the ranibizumab group IL-6 intensity was the lowest. The TL group did not significantly differ from the GnRHA and cabergoline groups regarding IL-6 expression. Ovarian VEGF expression was significantly lower in all treatment groups. For the TL, ranibizumab, and cabergoline groups VEGF intensity was similar. Tocilizumab may be a new strategy for preventing ovarian hyperstimulation syndrome by inhibition of IL-6.

Chinese abstract

该研究目的是探讨白介素-6（IL-6）阻滞剂托珠单抗对卵巢过度刺激大鼠模型的疗效，并比较雷珠单抗、促性腺激素释放激素（GnRHA）及卡麦角林间的疗效。47只大鼠随机分成以下7组：1：卵巢过度刺激（OHS）组；2：OHS+GnRHA组；3：OHS+雷珠单抗组；4：OHS+卡麦角林组；5：OHS+低剂量托珠单抗（TL）组；6：OHS+高剂量TL组；7：假处理组。在OHS各组中，只有雷珠单抗组大鼠卵巢重量明显降低。与OHS组和其他治疗组相比，GnRH组雌激素水平明显降低。与OHS组相比，雷珠单抗组、卡麦角林组和TL组孕激素水平明显降低且所有治疗组中卵巢黄体数量均降低，托珠单抗组黄体计数最低。各治疗组IL-6强度明显低于OHS组，雷珠单抗组最低。就IL-6表达情况而言，TL组与GnRHA组、卡麦角林组间无明显差别。卵巢血管内皮生长因子（VEGF）在所有治疗组中均显著性低表达。对于IL、雷珠单抗及卡麦角林组，VEGF表达强度相似。托珠单抗通过抑制IL-6表达可能是预防卵巢过度刺激综合征发生的一种新方法。

Keywords:

• Endometriosis
• IL-6
• rat
• tocilizumab

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material available online

Supplementary Graphics 1 and 2