Critical paracrine interactions between TNF-α and IL-10 regulate lipopolysaccharide-stimulated human choriodecidual cytokine and prostaglandin E2 production

T.A. Sato, Jeffrey Keelan, M.D. Mitchell

    Research output: Contribution to journalArticle

    90 Citations (Scopus)

    Abstract

    Increased production of PGs by gestational membranes is believed to be a principal initiator of term and preterm labor. Intrauterine infection is associated with an inflammatory response in the choriodecidua characterized by elevated production of cytokines and PGs. The precise physiological significance of enhanced choriodecidual cytokine production in the mechanism of preterm labor remains uncertain. These studies were undertaken to dissect the roles and regulation of endogenous cytokines in regulating PG production by human choriodecidua. We used LPS treatment of human choriodecidual explants as our model system. In choriodecidual explant cultures, LPS (5 mug/ml) induced a rapid increase in TNF-alpha production, peaking at 4 h. In contrast, IL-10, IL-1beta, and PGE(2) production rates peaked 8, 12, and 24 h, respectively, after LPS stimulation. Immunoneutralization studies indicated that TNF-alpha was a primary regulator of IL-1beta, IL-10, and PGE(2) production, while IL-1beta stimulated only PGE(2) production. Neutralization of endogenous IL-10 resulted in increased TNF-alpha and PGE(2) production. IL-10 treatment markedly decreased TNF-alpha and IL-1beta production, but had no effect on PGE(2) production. Taken together, these results demonstrate that the effects of LPS on choriodecidual cytokine and PG production are modulated by both positive and negative feedback loops. In the setting of an infection of the intrauterine, TNF-alpha may be a potential target for treatment intervention; IL-10 could be one such therapeutic.
    Original languageEnglish
    Pages (from-to)158-166
    JournalThe Journal of Immunology
    Volume170
    Issue number1
    DOIs
    Publication statusPublished - 2003

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