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.
Mitchell
Murray D
MD
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
Simpson
Kerryn L
KL
Keelan
Jeffrey A
JA
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