Levonorgestrel modulates innate immune activation in human endocervical epithelium and monocytes during Chlamydia trachomatis infection

ProblemOur group has previously shown that baboons with a levonorgestrel-releasing intrauterine system (LNG-IUS) have delayed clearance of Chlamydia trachomatis (Ct). Based on this result, we hypothesized that LNG results in changes to development of the immune response by epithelial and resident innate immune cells. Method of StudyUsing the end1 endocervical cell line or the THP.1 monocyte-like cell line, cells were exposed to increasing levels of progesterone (P4) or a dose of LNG representative of LNG in reproductive tract tissues of women with an LNG-IUS. Ct was used at an MOI of 1 and supernatants were collected for ELISA at 48 hours post-infection. Select nuclear receptors were inhibited to determine which receptor contributed to LNG-mediated immunosuppression. ResultsCervical epithelial cells infected with Ct expressed IL-1{beta} when treated with vehicle control. P4 further increased IL-1{beta} expression during Ct infection, while LNG decreased IL-1{beta} expression. Treatment with the androgen receptor blocker ailanthone prevented LNG-mediated immunosuppression. ConclusionsLNG in the presence of increasing P4 suppresses IL-1{beta} production in response to Ct infection in vitro. This appears to be mediated at least in part by the androgen receptor. This has implications for women with LNG-IUS at high risk for sexually transmitted infections.