{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:02:17Z","timestamp":1776924137993,"version":"3.51.2"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,12,14]],"date-time":"2004-12-14T00:00:00Z","timestamp":1102982400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p><jats:bold>Problem:\u2002<\/jats:bold> Previous data have shown \u2018danger\u2019 signals, such as bacterial lipopolysaccharide (LPS) acting via toll\u2010like (tlr) receptors are required for early pregnancy failure in several murine abortion models. Indeed, the abortion rate increased in the CBA\u2003\u00d7\u2003DBA\/2 model after a gestation day (gd) 7.5 injection of tumour necrosis factor (TNF)\u2010<jats:italic>\u03b1<\/jats:italic>\u2003+\u2003interferon (IFN)\u2010<jats:italic>\u03b3<\/jats:italic> only if the LPS\u2010tlr signalling pathway was intact. High rates of cytokine\u2010boosted abortion &gt;80% loss can be achieved in certain animal colonies, that have a high endogenous (spontaneous) rate of resorption (30\u201350%). A specific role for LPS has been postulated to determine both the endogenous and cytokine\u2010boosted losses.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> To test the role of LPS in spontaneous and cytokine\u2010boosted abortions, recombinant TNF\u2010<jats:italic>\u03b1<\/jats:italic>\u2003+\u2003IFN\u2010<jats:italic>\u03b3<\/jats:italic>, and LPS were injected in different doses and sequences intraperitoneally (i.p.) into CBA\u2003\u00d7\u2003DBA\/2 mated mice in the Toronto General Research Institute animal facility where the endogenous abortion rate is &lt;30%. The effects of poly IC, a tlr3 agonist that induces IFN\u2010<jats:italic>\u03b3<\/jats:italic> that can reverse LPS\u2010induced tolerance, and effects of anti\u2010MD\u20101 on TNF\u2010<jats:italic>\u03b1<\/jats:italic> induction by LPS, poly IC, CPG, or HSP in vitro were also examined.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> A high endogenous rate of loss similar to that seen in Clamart could be achieved by increasing exposure to LPS on the morning after mating (gd 0.5). The magnitude by which the abortion rate could be increased by an i.p. injection of 2000\u2003u TNF\u2010<jats:italic>\u03b1<\/jats:italic>\u2003+\u20031000\u2003u IFN\u2010<jats:italic>\u03b3<\/jats:italic> on gd 7.5 was independent of the endogenous rate of loss, and could not be increased by doubling the dose. One microgram of LPS given on day 7.5 achieved a similar rate of loss, and if given with the cytokines, synergistically boosted the rate of loss to near Clamart rates. LPS given 1\u2003day prior to the cytokines abrogated the cytokine effect, whereas LPS given day 0.5 had no significant effect on the response to day 7.5 cytokine injection. Blocking MD\u20101 inhibited TNF\u2010<jats:italic>\u03b1<\/jats:italic> stimulation by poly IC, LPS, CPG, or HSP <jats:italic>in vitro<\/jats:italic>, and reduced abortion rates. Poly IC did not avert LPS\u2010type tolerance effects <jats:italic>in vivo<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Conclusions:\u2002<\/jats:bold> High endogenous rates of abortion in the CBA\u2003\u00d7\u2003DBA\/2 model may be explained by exposure to LPS at the time of mating. Increased rates of loss triggered by cytokines later in pregnancy may depend on increased absorption of LPS from intestinal flora.<\/jats:p>","DOI":"10.1111\/j.1600-0897.2004.00237.x","type":"journal-article","created":{"date-parts":[[2004,12,14]],"date-time":"2004-12-14T16:20:53Z","timestamp":1103041253000},"page":"370-378","source":"Crossref","is-referenced-by-count":61,"title":["Ecology of Danger\u2010dependent Cytokine\u2010boosted Spontaneous Abortion in the CBA\u2003\u00d7\u2003DBA\/2 Mouse Model. I. 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