Context: Decidual neutrophil infiltration complicates spontaneous abortions associated with inflammation and hemorrhage. Transendothelial neutrophil migration into inflamed tissues involves interleukin-8 (IL-8)-mediated chemoattraction then neutrophil attachment to endothelial cell-expressed intercellular adhesion molecule-1 (ICAM-1).

Objective: To assess IL-8 and ICAM-1 regulation in decidual inflammation and hemorrhage, effects of the pro-inflammatory cytokines, tumor necrosis factor- (TNF-) and interleukin-1 (IL-1), and the hemostatic, pro-inflammatory cytokine thrombin were measured on IL-8 expression in first trimester decidual cells (DCs), whereas ICAM-1 immunostaining was compared in normal, inflamed and hemorrhagic first trimester decidua.

Design: Immunohistochemistry of human decidua and in vitro treatment of human decidual cells

Setting: Academic Medical Center

Intervention:. DCs were passaged until leukocyte (CD45-free by FACS) then incubated with estradiol (E₂) or with medroxyprogesterone acetate (MPA) alone or with TNF- or IL-1 or thrombin. Normal, inflamed and hemorrhagic decidua were immunostained for ICAM-1 and the neutrophil marker CD 14

Main Outcome Measure: ICAM-1 IL-8 levels in DC-conditioned media were assessed by ELISA and immunoblotting; IL-8 mRNA levels were measured by quantitative RT-PCR.

Results: ICAM-1 immunostaining was similar in normal or inflamed or hemorrhagic decidua. In cultured DCs, optimal concentrations of IL-1, TNF- and thrombin elevated secreted IL-8 levels by 1083 (± 261)-fold and 370 (± 77)-fold and 45 (± 15)-fold, respectively (mean ± SEM, P < 0.05, n = 8). The effects were dose-dependent and unaffected by MPA. Western blotting confirmed the ELISA results and corresponding effects on IL-8 mRNA levels were observed.

Conclusions: Cytokine/thrombin-enhanced decidual cell IL-8 expression interacts with constitutively expressed ICAM-1 in decidual endothelium to modulate neutrophil trafficking into hemorrhagic and inflamed first trimester decidua.