Jiraphorn Issara-AmphornSaowapha SurawutNavaporn WorasilchaiArthid Thim-UamMalcolm FinkelmanAriya ChindampornTanapat PalagaNattiya HirankarnPrapaporn PisitkunAsada LeelahavanichkulChulalongkorn UniversityFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityFaculty of Medicine, Thammasat UniversityInterdisciplinary and International ProgramCenter of Excellence in Immunology and Immune-mediated DiseasesAssociates of Cape Cod, Inc.Faculty of Graduate Studies2019-08-282019-08-282018-06-01Journal of Innate Immunity. Vol.10, No.3 (2018), 189-201166281281662811X2-s2.0-85041607504https://repository.li.mahidol.ac.th/handle/20.500.14594/46650© 2018 S. Karger AG, Basel. We investigated the influence of spontaneous gut leakage upon polymicrobial sepsis in a lupus model with Fc gamma receptor IIb-deficient (FcGRIIb-/-) mice aged 8 and 40 weeks, as representing asymptomatic and symptomatic lupus, respectively. Spontaneous gut leakage, determined by (i) the presence of FITC-dextran, (ii) elevated serum endotoxin, and (iii) elevated serum (1→3)-β-D-glucan (BG), was demonstrated in symptomatic lupus but not in the asymptomatic group. In parallel, spontaneous gut leakage, detected by elevated serum BG without fungal infection, was demonstrated in patients with active lupus nephritis. Gut leakage induced by dextran sulfate solution (DSS) or endotoxin administration together with BG or endotoxin alone, but not BG alone, enhanced the severity of cecal ligation and puncture (CLP) sepsis more prominently in 8-week-old FcGRIIb-/- mice. Additionally, the bone marrow-derived macrophages of FcGRIIb-/- mice produced higher cytokine levels when coexposed to endotoxin and BG, when compared to wild-type mice. In summary, spontaneous gut leakage was demonstrated in symptomatic FcGRIIb-/- mice and the induction of gut permeability worsened sepsis severity. Gut translocation of endotoxin and BG had a minor effect on wild-type mice, but the synergistic effect of BG and endotoxin was prominent in FcGRIIb-/- mice. The data suggest that therapeutic strategies addressing gut leakage may be of interest in sepsis conditions in patients with lupus.Mahidol UniversityMedicineArticleSCOPUS10.1159/000486321