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Interleukin 4 and interleukin 13 downregulate the lipopolysaccharide-mediated inflammatory response by human gestation-associated tissues† / Aled, Bryant; Ruth, Jones; Catherine, Thornton; Sian-eleri, Owens
Biology of Reproduction, Volume: 96, Issue: 3, Pages: 576 - 586
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This is a pre-copyedited, author-produced version of an article accepted for publication in Biology of Reproduction following peer review. The version of record is available online at: 10.1095/biolreprod.116.145680Download (552.68KB)
Local and systemic inflammation is a key feature of preterm and term labour and delivery. Pro-inflammatory mediators are produced by gestation-associated tissues in response to a broad range of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Interleuki...
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Local and systemic inflammation is a key feature of preterm and term labour and delivery. Pro-inflammatory mediators are produced by gestation-associated tissues in response to a broad range of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). Interleukin (IL)-4, IL-10 and IL-13 are well recognised anti-inflammatory cytokines and might have potential as anti-inflammatory therapies to prevent preterm birth. The objective of this study was to determine if IL-4 and IL-13 exert anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines produced by human term gestation-associated tissues (placenta, choriodecidua and amnion). Both IL-4 and IL-13 reduced LPS-stimulated IL-1β and macrophage inflammatory protein (MIP)-1α with this effect diminishing with delay to exposure to IL-4 or IL-13; there was no effect on LPS-stimulated prostaglandin production. IL-4 receptor α (IL-4Rα) was expressed throughout the placenta, choriodecidua and amnion, and the inhibitory effects of IL-4 and IL-13 were IL-4Rα-dependent. A combination of IL-4 and IL-13 did not enhance the anti-inflammatory potential of either cytokine; however, a combination of IL-4 and IL-10 had a greater anti-inflammatory effect than either cytokine alone. These findings demonstrate that human term gestation-associated tissues are responsive to the anti-inflammatory cytokines IL-4 and IL-13, which could down-regulate LPS induced cytokine production in these tissues. Anti-inflammatory cytokines might offer an adjunct to existing therapeutics to prevent adverse obstetric outcome.
inflammation, pregnancy, placenta, interleukin-4, interleukin-13
Swansea University Medical School