Paradoxical proinflammatory actions of interleukin-10 in human amnion: potential roles in term and preterm labour.
IL-10 is regarded predominantly as an inhibitor of cell-mediated inflammatory reactions. As such, it has been suggested that IL-10 could have therapeutic potential, including the treatment of preterm labor. Using explant cultures of gestational membranes we have found that IL-10 does indeed exert anti-inflammatory properties in choriodecidua, but that in the adjacent amnion it has remarkable pro-inflammatory actions. Amnion prostaglandin (PG) E(2) production was significantly increased following 24-h treatment with IL-10 (5-100 ng/mL). Production of IL-8 also showed a significant stimulation at 100 ng/mL IL-10. In contrast, choriodecidual production of IL-8 and tumor necrosis factor (TNF)-alpha was dramatically inhibited by IL-10, confirming the ability of this tissue to exhibit a classical IL-10 response. IL-10 retained its stimulatory actions on amnion in the presence of IL-1beta and TNF-alpha stimulation. These findings suggest that the fetal membranes can exhibit opposing responses to IL-10, depending on whether the inflammatory insult occurs at the maternal or fetal face. While inflammatory reactions are negatively regulated by IL-10 in choriodecidua, if the pathogen reaches the amnion and threatens the fetus, pro-inflammatory reactions may predominate to ensure successful labor to spare and protect the fetus.
Liggins Institute, Department of Pharmacology, University of Auckland, Faculty of Medical and Health Sciences, Private Bag 92019, Auckland, New Zealand. m.mitchell@auckland.ac.nz
Murray D
MD
Mitchell
Kerryn L
KL
Simpson
Jeffrey A
JA
Keelan
D000650:Amnion / Q000378:metabolism*; D002823:Chorion / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D003656:Decidua / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007743:Labor, Obstetric / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000503:physiopathology; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015232:Dinoprostone