{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:45:19Z","timestamp":1770140719174,"version":"3.49.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p><jats:bold>Importance:<\/jats:bold> Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis.<\/jats:p><jats:p><jats:bold>Design:<\/jats:bold> A retrospective cohort study from previously collected data.<\/jats:p><jats:p><jats:bold>Setting:<\/jats:bold> Individual patient data were gathered from three different international datasets.<\/jats:p><jats:p><jats:bold>Participants:<\/jats:bold> Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy.<\/jats:p><jats:p><jats:bold>Exposure:<\/jats:bold> None.<\/jats:p><jats:p><jats:bold>Main Outcome(s) and Measure(s):<\/jats:bold> The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, <jats:italic>p<\/jats:italic> &amp;lt; 0.01], but no differences in sex (41 vs. 43% female, <jats:italic>p<\/jats:italic> = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), vasoactive drug use 79 vs. 66% (<jats:italic>p<\/jats:italic> = 0.13), and mortality 4.6 vs. 34.1% (<jats:italic>p<\/jats:italic> &amp;lt; 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng\/dl in MIS-C and 1,432 (122, 6,886) ng\/dl in sepsis (<jats:italic>p<\/jats:italic> &amp;lt; 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52\/66 (78.8%) patients had shock in MIS-C group, and 29\/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock.<\/jats:p><jats:p><jats:bold>Conclusions and Relevance:<\/jats:bold> IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don't discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases.<\/jats:p>","DOI":"10.3389\/fped.2021.756083","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T06:58:25Z","timestamp":1636959505000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Comparison of Interleukin-6 Plasma Concentration in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Pediatric Sepsis"],"prefix":"10.3389","volume":"9","author":[{"given":"Franco","family":"Diaz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ra\u00fal","family":"Bustos 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