Human chorionic gonadotropin (hCG) sub-chronic administration mediated MMP-9 activities and cytokine association deteriorate experimental autoimmune encephalomyelitis (EAE) condition in mice model

Abstract

We investigated the role of sub-chronic administration of human chorionic gonadotropin (hCG) in an experimental autoimmune encephalomyelitis (EAE) mice model as a multiple sclerosis (MS) model. MS is a disease of malfunctioned immune system where infiltrating immune cells are stimulated by matrix metalloproteinase (MMP) activation and cause blood？brain barrier disruption followed by the destruction of myelin sheath by concurrent activation of cytokines. hCG is responsible for the expression and activation of MMPs and regulation of cytokines in different cells. Mice were implanted with the osmotic pump containing hCG and luteinizing hormone (LH) which maintain their release for 4？weeks with constant velocity. The activities of MMP-9 and NADPH oxidase and the levels of cytokines were measured in the plasma and the CNS tissues. The hCG treated EAE mice showed a decrease in body weights, increased mortality, accelerated onset stage and amplified EAE severity. MMP-9 activity was increased significantly in the EAE+hCG group compared to EAE group in both CNS and plasma. We also found increased activity of NADPH oxidase in plasma at onset stage and in brain tissues at day 38. IL-6 and IL-4 levels in brain tissue were found significantly higher in EAE+hCG group than in EAE group. EAE+LH group mice showed early onset patterns like EAE+hCG group and MMP-9 and NADPH oxidase levels were higher than EAE group, but cytokines levels were not significantly different from EAE group. We suggest that hCG treatment should be considered carefully as multiple or constant hCG treatment could exacerbate aggravation of MS induction and clinical symptoms. ？ 2016, The Korean Society of Pharmaceutical Sciences and Technology.