title: Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm labor in mice.
abstract: IL-10 is highly expressed in the uterus and placenta and is implicated in controlling inflammation-induced pathologies of pregnancy. To investigate the role of IL-10 in regulating preterm labor, the response of IL-10 null mutant mice to low-dose LPS in late gestation was evaluated. When IL-10 null mutant C57BL/6 (IL-10(-/-)) and control (IL-10(+/+)) mice were administered LPS on day 17 of pregnancy, the dose of LPS required to elicit 50% preterm fetal loss was 10-fold lower in IL-10(-/-) mice than in IL-10(+/+) mice. Surviving fetuses in IL-10(-/-) mice exhibited fetal growth restriction at lower doses of LPS than IL-10(+/+) mice. Marked elevation of LPS-induced immunoactive TNF-alpha and IL-6 was evident in the serum, uterus, and placenta of IL-10(-/-) mice, and TNF-alpha and IL-6 mRNA expression was elevated in the uterus and placenta, but not the fetus. Serum IL-1alpha, IFN-gamma, and IL-12p40 were increased and soluble TNFRII was diminished in the absence of IL-10, with these changes also reflected in the gestational tissues. Administration of rIL-10 to IL-10(-/-) mice attenuated proinflammatory cytokine synthesis and alleviated their increased susceptibility to preterm loss. Exogenous IL-10 also protected IL-10(+/+) mice from fetal loss. These data show that IL-10 modulates resistance to inflammatory stimuli by down-regulating proinflammatory cytokines in the uterus and placenta. Abundance of endogenous IL-10 in gestational tissues is therefore identified as a critical determinant of resistance to preterm labor, and IL-10 may provide a useful therapeutic agent in this common condition.
authors.affiliation: Research Centre for Reproductive Health and Department of Obstetrics and Gynecology, University of Adelaide, Adelaide, SA 5005, Australia. sarah.robertson@adelaide.edu.au
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Robertson
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Skinner
authors.forename: Alison S
authors.initials: AS
authors.lastname: Care
mesh_terms: D000818:Animals; D005260:Female; D007118:Immunoassay; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D007752:Obstetric Labor, Premature / Q000139:chemically induced* / Q000276:immunology*; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D021122:Protein Subunits / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014599:Uterus / Q000276:immunology / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D008070:Lipopolysaccharides; D021122:Protein Subunits; D012333:RNA, Messenger; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma