REGULATION OF HUMAN DECIDUAL CELL MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA (MIP-1-ALPHA) PRODUCTION BY INFLAMMATORY CYTOKINES

PROBLEM: Inflammation of human gestational tissues is a key pathophysi ologic event in the genesis of infection-associated preterm labor. Hum an gestational tissues produce several inflammatory cytokines after st imulation with bacterial products. These include interleukin-1 beta (I L-1 beta), tumor necrosis factor-alpha (TNF alpha), and IL-6. Another class of cytokines includes chemokines of the ''C-C'' subclassificatio n such as macrophage inflammatory protein-1 alpha (MIP-1 alpha). The p urpose of this study was to determine whether cultured human decidual cells produce MIP-la: in response to other inflammatory cytokines. MET HODS: Various concentrations of IL-1 beta, TNF alpha, IL-6, and IL-4 w ere incubated with confluent monolayer cultures of decidual cells isol ated from normal term placentae for 16 h at 37 degrees C, and MIP-1 al pha concentrations in culture supernatants were measured by ELISA. RES ULTS: We found that incubation of decidual cells with IL-1 beta, TNF a lpha, and IL-4 resulted in significant concentration-dependent increas es in MIP-1 alpha production. IL-6 had no effect on MIP-1 alpha produc tion. CONCLUSIONS: Our data are the first to show that human decidual cells in culture produce MIP-1 alpha in response to other inflammatory cytokines. We suggest that decidual cell production of MIP-1 alpha is an important early event in the pathophysiology of infection-associat ed preterm labor.