Tocilizumab Inhibits Interleukin-6-Mediated Matrix Metalloproteinase-2 and -9 Secretions from Human Amnion Cells in Preterm Premature Rupture of Membranes

Abstract

Background/Aims: In the present study, we investigated the participation of inflammatory cytokine-induced mediated matrix metalloproteinase (MMP) expressions and inhibition of interleukin (IL)-6-induced MMP secretion in amniotic epithelial cells by tocilizumab. Methods: To investigate the role of MMP expressions, immunohistochemical staining was performed using membranes obtained from 10 patients with preterm premature rupture of membranes (PPROM) and from 10 patients who underwent a nonlabor cesarean section. We also investigated the regulation of MMP expression by inflammatory cytokines in human amnion cells. Results: Immunohistochemical staining showed a significantly higher expression of MMP-2 and -9 in PPROM. Treatment of cultured WISH and primary amniotic epithelial cells with 10^–8 or 10^–7M IL-6 or tumor necrosis factor (TNF)-α clearly increased the secretion of MMP-2 and -9. Treatment with 10^–8M TNF-α or IL-6 significantly increased the invasion of WISH or primary amniotic epithelial cells, respectively, compared with the control. At a low concentration of 1 μg/ml, tocilizumab (anti-human IL-6 receptor monoclonal antibody) inhibited the IL-6-induced MMP secretion. Conclusions: This paper is the 1st report of tocilizumab inhibiting IL-6-induced MMP-2 and MMP-9 secretions from human amnion cells in PPROM.