RESUMEN
Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 have crucial role in the pathogenesis of endometriosis. In this study, we investigated the immune-modulatory role of humanized anti-IL-6 receptor monoclonal antibodies in the treatment of endometriosis. This is a prospective, randomized, controlled, blinded study in which Sprague Dawley rats were used as animal model of endometriosis. Animals were randomly divided into two groups, a test group which received tocilizumab (Actemra; Roche, Switzerland) and a control group which received saline. Afterwards, a comparison was done between the eutopic and ectopic endometrium that was excised from both groups, histopathologically and immune-histochemically. Histopathologic assessment and immune-histochemical staining were performed using antibodies against IL-6. Tocilizumab significantly suppressed the volume of endometriotic lesions compared with non-treated rats (P = 0.006) and atrophied the ectopic endometrial-like epithelium (in 42.8% of treated rats vs 0% in the control group). Tocilizumab also decreased the anti-IL-6 receptor immune-histochemical staining intensity in ectopic endometrium (from non to +++ in the test group vs ++ or more in the control group), with no apparent difference in the eutopic one reflecting the down-regulation of IL-6-producing cells in ectopic endometriotic lesions. In rats with induced endometriosis, anti-IL-6 receptor monoclonal antibodies could offer a new horizon of usage of this immune-modulatory biologic drug, used in other autoimmune diseases, in treatment of endometriosis.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Endometriosis/tratamiento farmacológico , Endometriosis/patología , Receptores de Interleucina-6/antagonistas & inhibidores , Animales , Biomarcadores , Endometriosis/etiología , Femenino , Inmunohistoquímica , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: To evaluate the value of vaginal progesterone therapy for reduction of preterm labor in asymptomatic women with twin pregnancies and sonographic short cervix. METHODS: This randomized controlled study was conducted in Mansoura University Hospital and private practice settings in Mansoura, Egypt. Of 322 women with dichorionic twin pregnancy, 250 asymptomatic women with cervical length of 20-25 mm at 20-24 weeks of gestation were included in the study. All women were randomly divided into two groups; the study group (n = 125) received vaginal progesterone suppositories in a dose of 400 mg daily starting at 20-24 weeks of gestation while the control group (n = 125) received no treatment. The primary outcome measure was preterm labor before 34 weeks of gestation and the secondary outcome measures were neonatal respiratory distress syndrome (RDS) and early neonatal death (END). RESULTS: 224 women (116 in the study group and 108 in the control group) were subjected to final analysis. The duration of pregnancy was significantly longer in the study group and the incidence of preterm labor before 34 and 32 weeks of gestation was significantly lower in the study group. The neonatal morbidities and mortality were significantly lower in the study group as shown by lower incidence of very low (<1500 gm) birth weight, neonatal RDS, the need for mechanical ventilation and END. CONCLUSIONS: Vaginal progesterone administration in asymptomatic twin pregnancies with sonographic short cervix (20-25 mm) at 20-24 weeks of gestation is effective and safe treatment for reducing the incidence of preterm labor with subsequent reduction in the neonatal morbidities and mortality associated with preterm birth.