Department of Gynecology Obstetrics II and Reproductive Medicine, Sorbonne Paris Cité, Faculté de Médecine, Université Paris Descartes, AP-HP, Hôpital Cochin, 75679 Paris, France.
Hum Reprod. 2013 Aug;28(8):2126-33. doi: 10.1093/humrep/det238. Epub 2013 Jun 5.
Are interleukin-33 (IL-33) serum levels higher in women with uterine leiomyoma compared with controls without leiomyoma?
Serum IL-33 is elevated in women with uterine leiomyoma and correlated with features of uterine leiomyoma tumour burden, namely fibroid number, size and weight.
Uterine leiomyomas are the most common benign tumours in premenopausal women associated with major tissue fibrosis. IL-33 is a cytokine involved in fibrotic disorders. The potential role of IL-33 in leiomyoma has not been reported before.
STUDY DESIGN, SIZE, DURATION: This is a prospective laboratory study conducted in a tertiary-care university hospital between January 2005 and December 2010. We investigated non-pregnant, 42-year-old patients (n = 151) during surgery for a benign gynaecological condition.
PARTICIPANTS/MATERIALS, SETTING, METHODS: After complete surgical exploration of the abdominopelvic cavity, 59 women with histologically proved uterine leiomyoma and 92 leiomyoma-free control women were enrolled. Women with endometriosis or past history of ovarian malignancy and borderline tumours were not included. The control group included women with benign ovarian cysts, paratubal cysts or tubal defects without any evidence of uterine leiomyoma. For each patient, a structured questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery. Serum samples were obtained in the month preceding the surgical procedures according to the menstrual phase or hormonal therapy. IL-33 was measured in sera by enzyme-linked immunosorbent assay, and correlation of IL-33 concentration with the extent and severity of the disease was investigated.
IL-33 was detected in 32 (54.2%) women with leiomyoma and 18 (19.6%) controls (P < 0.001). Serum IL-33 was higher in women with leiomyoma (median, 140.1 pg/ml; range, 7.5-2247.7) than in controls (median, 27.8 pg/ml; range, 7.5-71.6; P = 0.002). We found positive correlations between serum IL-33 concentration and leiomyoma features, such as fibroid weight (r = 0.630; P = 0.001) and size (r = 0.511; P = 0.018) and the number of fibroids (r = 0.503; P = 0.003).
LIMITATIONS, REASONS FOR CAUTION: There was a possible selection bias due to inclusion of only surgical patients. Therefore our control group consisted of women who underwent surgery for benign gynaecological conditions. This may lead to biases stemming from the fact that certain of these conditions, such as tubal infertility or ovarian cysts, might be associated with altered serum IL-33 levels.
We demonstrate for the first time that elevated serum IL-33 levels are associated with the existence of uterine leiomyoma. However, even if an association does not constitute proof of cause and effect, investigating the mechanisms that underlie fibrogenesis associated with leiomyomas is a step towards understanding this enigmatic disease. This study opens the doors to future, more mechanistics studies to establish the exact role of IL-33 in uterine leiomyomas pathogenesis.
STUDY FUNDING/COMPETING INTEREST(S): No funding, no conflict of interest.
与没有子宫肌瘤的对照组相比，患有子宫肌瘤的女性血清白细胞介素-33（IL-33）水平是否更高？
患有子宫肌瘤的女性血清 IL-33 水平升高，并与子宫肌瘤肿瘤负担的特征相关，即肌瘤数量、大小和重量。
子宫肌瘤是绝经前妇女最常见的良性肿瘤，与主要组织纤维化有关。IL-33 是一种参与纤维化疾病的细胞因子。IL-33 在子宫肌瘤中的潜在作用以前尚未报道过。
研究设计、规模、持续时间：这是一项在 2005 年 1 月至 2010 年 12 月期间在三级保健大学医院进行的前瞻性实验室研究。我们在手术期间调查了 42 岁的非妊娠患者（n = 151）良性妇科疾病。
参与者/材料、设置、方法：在完成对腹盆腔的彻底手术探查后，纳入了 59 名经组织学证实患有子宫肌瘤的女性和 92 名无子宫肌瘤的对照组女性。不包括子宫内膜异位症或卵巢恶性肿瘤病史和交界性肿瘤的患者。对照组包括患有良性卵巢囊肿、附件囊肿或输卵管缺陷的女性，且没有任何子宫肌瘤的证据。对于每位患者，由外科医生在手术前一个月进行的面对面访谈中完成了一份结构化问卷。根据月经周期或激素治疗，在手术前一个月获得血清样本。通过酶联免疫吸附试验测量血清中的 IL-33，并研究 IL-33 浓度与疾病严重程度和严重程度的相关性。
在 151 名患者中，32 名（54.2%）患有子宫肌瘤，18 名（19.6%）为对照组（P <0.001）。患有子宫肌瘤的女性血清 IL-33 水平高于对照组（中位数，140.1 pg/ml；范围，7.5-2247.7）（中位数，27.8 pg/ml；范围，7.5-71.6；P = 0.002）。我们发现血清 IL-33 浓度与子宫肌瘤特征之间存在正相关，例如肌瘤重量（r = 0.630；P = 0.001）和大小（r = 0.511；P = 0.018）以及肌瘤数量（r = 0.503；P = 0.003）。
局限性、谨慎的原因：由于仅纳入了手术患者，因此存在可能的选择偏倚。因此，我们的对照组包括因良性妇科疾病接受手术的女性。这可能导致某些情况下的偏差，例如输卵管不孕或卵巢囊肿，这些情况可能与血清 IL-33 水平改变有关。
我们首次证明，升高的血清 IL-33 水平与存在子宫肌瘤有关。然而，即使关联不能构成因果关系的证据，研究与子宫肌瘤相关的纤维化发生相关的机制也是朝着理解这种神秘疾病迈出的一步。这项研究为未来更具机制的研究打开了大门，以确定 IL-33 在子宫肌瘤发病机制中的确切作用。
研究资金/利益冲突：无资金，无利益冲突。
