{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:54:07Z","timestamp":1793364847839,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Neutrophils are critical mediators of the innate immune response, and their antimicrobial functions are tightly regulated by a myriad of cytokines. Interleukin-6 (IL-6) is known to be essential for an effective immune response; however, how varying IL-6 concentrations affect the neutrophil response remains poorly understood. Because IL-6 concentrations can vary greatly across different disease states, we investigated the concentration dependent effects of IL-6 on the neutrophil response to diverse bacterial pathogens using an infection-on-a-chip microfluidic device. We found that a high exogenous IL-6 concentration (100 ng\/mL) reduced neutrophil extravasation, migration speed, and displacement compared to conditions without exogenous IL-6. In contrast, a lower exogenous IL-6 concentration (10 ng\/mL) produced pathogen-specific effects on neutrophil extravasation: exogenous IL-6 increased neutrophil extravasation in response to\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    , did not change in response to\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    , and decreased in response to\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    relative to controls. We then determined the potential endothelial cell contributions to these responses. We found that increasing IL-6 concentration resulted in decreased VE-cadherin expression and that 100 ng\/mL exogenous IL-6 resulted in lower ICAM-1 expression than 10 ng\/mL exogenous IL-6 in an endothelium exposed to\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    . Together, these results demonstrate that IL-6 exerts concentration- and pathogen-dependent effects on neutrophil recruitment and migration, supporting a dual role for IL-6 as both pro-inflammatory and anti-inflammatory, with higher IL-6 concentrations resulting in a more anti-inflammatory neutrophil response.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1783843","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:34:35Z","timestamp":1771997675000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Interleukin-6 regulates the neutrophil response to diverse bacteria"],"prefix":"10.3389","volume":"17","author":[{"given":"Justin M.","family":"Owens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah 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