{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:23:16Z","timestamp":1779117796711,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,7,19]],"date-time":"2015-07-19T00:00:00Z","timestamp":1437264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Combined inhibition of complement and CD14 is known to attenuate bacterial-induced inflammation, but the dependency of the bacterial load on this effect is unknown. Thus, we investigated whether the effect of such combined inhibition on Escherichia coli- and Staphylococcus aureus-induced inflammation was preserved during increasing bacterial concentrations. Human whole blood was preincubated with anti-CD14, eculizumab (C5-inhibitor) or compstatin (C3-inhibitor), or combinations thereof. Then heat-inactivated bacteria were added at final concentrations of 5 \u00d7 104\u22121 \u00d7 108\/ml (E. coli) or 5 \u00d7 107\u22124 \u00d7 108\/ml (S. aureus). Inflammatory markers were measured using enzyme-linked immunosorbent assay (ELISA), multiplex technology and flow cytometry. Combined inhibition of complement and CD14 significantly (P &amp;lt; 0.05) reduced E. coli-induced interleukin (IL)-6 by 40\u201392% at all bacterial concentrations. IL-1\u03b2, IL-8 and macrophage inflammatory protein (MIP)-1\u03b1 were significantly (P &amp;lt; 0.05) inhibited by 53\u2013100%, and the effect was lost only at the highest bacterial concentration. Tumour necrosis factor (TNF) and MIP-1\u03b2 were significantly (P &amp;lt; 0.05) reduced by 80\u201397% at the lowest bacterial concentration. Monocyte and granulocyte CD11b were significantly (P &amp;lt; 0.05) reduced by 63\u201391% at all bacterial doses. Lactoferrin was significantly (P &amp;lt; 0.05) attenuated to the level of background activity at the lowest bacterial concentration. Similar effects were observed for S. aureus, but the attenuation was, in general, less pronounced. Compared to E. coli, much higher concentrations of S. aureus were required to induce the same cytokine responses. This study demonstrates generally preserved effects of combined complement and CD14 inhibition on Gram-negative and Gram-positive bacterial-induced inflammation during escalating bacterial load. The implications of these findings for future therapy of sepsis are discussed.<\/jats:p>","DOI":"10.1111\/cei.12645","type":"journal-article","created":{"date-parts":[[2015,4,24]],"date-time":"2015-04-24T05:09:39Z","timestamp":1429852179000},"page":"457-467","source":"Crossref","is-referenced-by-count":9,"title":["The anti-inflammatory effect of combined complement and CD14 inhibition is preserved during escalating bacterial load"],"prefix":"10.1093","volume":"181","author":[{"given":"Kjetil H","family":"Egge","sequence":"first","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Barratt-Due","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stig","family":"Nymo","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital and Faculty of Health Sciences, K. G. Jebsen TREC, University of Troms\u00f8, Troms\u00f8, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie K","family":"Lindstad","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Pharo","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Lau","sequence":"additional","affiliation":[{"name":"Research Laboratory, Nordland Hospital and Faculty of Health Sciences, K. G. Jebsen TREC, University of Troms\u00f8, Troms\u00f8, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terje","family":"Espevik","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebbe B","family":"Thorgersen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom E","family":"Mollnes","sequence":"additional","affiliation":[{"name":"Department of Immunology, Oslo University Hospital Rikshospitalet, and K. G. Jebsen IRC, University of Oslo, Oslo, Norway"},{"name":"Research Laboratory, Nordland Hospital and Faculty of Health Sciences, K. G. Jebsen TREC, University of Troms\u00f8, Troms\u00f8, Norway"},{"name":"Centre of Molecular Inflammation Research and Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,7,19]]},"reference":[{"key":"2021122010153890600_cei12645-bib-0001","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1378\/chest.11-0352","article-title":"Nationwide trends of severe sepsis in the 21st century (2000\u20132007)","volume":"140","author":"Kumar","year":"2011","journal-title":"Chest"},{"key":"2021122010153890600_cei12645-bib-0002","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s00134-009-1738-3","article-title":"The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe 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