Preeclampsia (PE), new-onset hypertension during pregnancy, is associated with chronic inflammation both in the placenta and systemically. PE is characterized by placental ischemia, which then results in the production and release of anti-angiogenic factors and inflammatory mediators. Inflammation in PE leads to placental, renal, and vascular damage, which contribute to the phenotype of hypertension and organ dysfunction during pregnancy. T cells, B cells, Natural Killer cells, and macrophages have all been shown to play a role in the inflammation present in the disease. T helper cells contribute to the chronic inflammation in PE. They also activate B cells, which produce agonistic autoantibodies against the angiotensin II type 1 receptor. Natural Killer cells are activated in PE and shift away from decidual Natural killer cells, which produce angiogenic factors, and toward cytotoxic Natural Killer cells, which contribute to tissue damage. Macrophages are polarized towards proinflammatory subtypes and contribute to tissue damage and inflammatory signaling in PE patients. As the immune system plays a role in the pathophysiology of the disease, it may be a potential target for therapeutic intervention to improve maternal and fetal outcomes during and following a PE pregnancy.

The role of the pneumococcal polysaccharide capsule is largely unclear for Streptococcus pneumoniae keratitis, an ocular inflammatory disease that develops as a result of bacterial infection of the cornea. In this study, capsule-deficient strains were compared to isogenic parent strains in their ability to adhere to human corneal epithelial cells. One isogenic pair was further used in topical ocular infection of mice to assess the contribution of the capsule to keratitis. The results showed that non-encapsulated pneumococci were significantly more adherent to cells, persisted in significantly higher numbers on mouse corneas in vivo, and caused significant increases in murine ocular IL9, IL10, IL12-p70, MIG, and MIP-1-gamma compared to encapsulated S. pneumoniae. These findings indicate that the bacterial capsule impedes virulence and the absence of capsule impacts inflammation following corneal infection.

Preeclampsia (PE) is characterized by maternal hypertension, fetal growth restriction (FGR), and increased inflammation and populations of cytotoxic NK cells (cNKs) and inflammatory T-Helper 17 cells (TH17s). Both cytotoxic NK cells and TH17 cells are heavily influenced via IL-1β signaling. Caspase 1 activity leads to the release of the inflammatory cytokine IL-1β, which is increased in women with PE. Therefore, we tested the hypothesis that the inhibition of Caspase 1 with VX-765 in rats with reduced uterine perfusion pressure (RUPP) will attenuate PE pathophysiology. On gestation day (GD) 14, timed pregnant Sprague–Dawley rats underwent the RUPP or Sham procedure and were separated into groups that received either vehicle or VX-765 (50 mg/kg/day i.p.). On GD19, MAP was measured via carotid catheter and blood and tissues were collected. Bio-Plex and flow cytometry analysis were performed on placental tissues. Placental IL-1β was increased in the RUPP rats vs. the Sham rats and treatment with VX-765 reduced IL-1β in the RUPP rats. Caspase 1 inhibition reduced placental cNKs and TH17s in RUPP rats compared to vehicle-treated RUPP rats. Increased MAP was observed in RUPP rats compared with Sham rats and was reduced in RUPP + VX-765 rats. Placental reactive oxygen species (ROS) were elevated in RUPP rats compared to Sham rats. VX-765 administration reduced ROS in treated RUPP rats. Caspase 1 inhibition increased the number of live pups, yet had no effect on fetal weight or placental efficiency in the treated groups. In conclusion, Caspase 1 inhibition reduces placental IL-1β, inflammatory TH17 and cNK populations, and reduces MAP in RUPP rats. These data suggest that Caspase 1 is a key contributor to PE pathophysiology. This warrants further investigation of Caspase 1 as a potential therapeutic target to improve maternal outcomes in PE.

IL-1R1 inhibition in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia lowered maternal blood pressure, reduced fetal reabsorptions, and improved fetal and placental growth. These effects were accompanied by restored systemic and placental immune balance but no improvement in vascular markers such as VEGF or preproendothelin. Thus, IL-1R1 blockade, including the clinical agent anakinra, is a promising therapeutic avenue that may require combination strategies for optimal benefit.