Essential Role for IL-10 in Resistance to Lipopolysaccharide-Induced Preterm Labor in Mice
- 1 October 2006
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 177 (7), 4888-4896
- https://doi.org/10.4049/jimmunol.177.7.4888
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-α and IL-6 was evident in the serum, uterus, and placenta of IL-10−/− mice, and TNF-α and IL-6 mRNA expression was elevated in the uterus and placenta, but not the fetus. Serum IL-1α, IFN-γ, 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.Keywords
This publication has 62 references indexed in Scilit:
- Maternal infection-induced white matter injury is reduced by treatment with interleukin-10American Journal of Obstetrics and Gynecology, 2004
- Defining the problem: the epidemiology of preterm birthBJOG: An International Journal of Obstetrics and Gynaecology, 2003
- Recent evidence associated with the condition of preterm prelabour rupture of the membranesCurrent Opinion in Obstetrics and Gynecology, 2003
- Interleukin-10 inhibition of interleukin-6 in human amniochorionic membrane: Transcriptional regulationAmerican Journal of Obstetrics and Gynecology, 1996
- Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance.JCI Insight, 1995
- Interleukin-10 gene knock-out mice: a model of chronic inflammationClinical Immunology and Immunopathology, 1995
- Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblastsPlacenta, 1994
- Interleukin‐10 controls interferon‐γ and tumor necrosis factor production during experimental endotoxemiaEuropean Journal of Immunology, 1994
- Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia.The Journal of Experimental Medicine, 1993
- Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.The Journal of Experimental Medicine, 1991