biostudies-literaturePalmer CDGreene FundDana Human Immunology AwardThrasher FoundationDefense Advanced Projects AgencyNIAID NIH HHSAmerican Recovery and Reinvestmant Act NIH Administrative SupplementNHLBI NIH HHSDARPANIHDartmouth Center for Medical Countermeasures Pilot ProjectNIGMS NIH HHS459-70https://www.ebi.ac.uk/biostudies/studies/S-EPMC3157902biostudies-literatureUnknown90(3)Detection and clearance of bacterial infection require balanced effector and resolution signals to avoid chronic inflammation. Detection of GNB LPS by TLR4 on m induces inflammatory responses, contributing to chronic inflammation and tissue injury. LXs and Rvs are endogenous lipid mediators that enhance resolution of inflammation, and their actions on primary human m responses toward GNB are largely uncharacterized. Here, we report that LXA(4), LXB(4), and RvD1, tested at 0.1-1 μM, inhibited LPS-induced TNF production from primary human m, with ATL and 17(R)-RvD1, demonstrating potent inhibition at 0.1 μM. In addition, 17(R)-RvD1 inhibited LPS-induced primary human m production of IL-7, IL-12p70, GM-CSF, IL-8, CCL2, and MIP-1α without reducing that of IL-6 or IL-10. Remarkably, when stimulJournal of leukocyte biology17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and live E. coli.PMC3157902R21 HL089659-01A1RO1 AI067353R01 AI067353P01 GM095467R21 HL0896593R01AI067353-05S1R01 GM038765R01GM038765P01GM095467Mancuso CJSerhan CNWeiss JPPalmer CDLevy OGuinan ECfalse17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and live E. coli.Detection and clearance of bacterial infection require balanced effector and resolution signals to avoid chronic inflammation. Detection of GNB LPS by TLR4 on m induces inflammatory responses, contributing to chronic inflammation and tissue injury. LXs and Rvs are endogenous lipid mediators that enhance resolution of inflammation, and their actions on primary human m responses toward GNB are largely uncharacterized. Here, we report that LXA(4), LXB(4), and RvD1, tested at 0.1-1 μM, inhibited LPS-induced TNF production from primary human m, with ATL and 17(R)-RvD1, demonstrating potent inhibition at 0.1 μM. In addition, 17(R)-RvD1 inhibited LPS-induced primary human m production of IL-7, IL-12p70, GM-CSF, IL-8, CCL2, and MIP-1α without reducing that of IL-6 or IL-10. Remarkably, when stimul2011-01-01T00:00:00Z2011 Sep2025-07-11T03:04:01.108Z2025-07-11T03:04:01.108ZS-EPMC31579022165323410.1189/jlb.0311145