Early Elevation in Random Plasma Il-6 After Severe Injury Is Associated With Development of Organ Failure

Abstract

Background Excessive pro-inflammatory activation following trauma plays a role in late morbidity and mortality including the development of multiple organ dysfunction syndrome (MODS). To date, identification of patients at risk has been challenging. Results from animal and human studies suggest that circulating IL-6, may serve as a biomarker for excessive inflammation. The purpose of this analysis was to determine the association of IL-6 to outcome in a multi-center developmental cohort and in a single-center validation cohort. Methods Severely injured patients with shock due to hemorrhage were evaluated within a multi-center developmental cohort (n=79). All had blood drawn within 12 hours of injury. Plasma IL-6 was determined by multiplex proteomic analysis. Clinical and outcome data were prospectively obtained. Within this developmental cohort, a plasma IL-6 level was determined for the subsequent development of MODS by developing a receiver operating curve (ROC) and defining the optimal IL-6 level using the Youden index. This IL-6 level was then evaluated within a separate validation cohort (n=56). Results A receiver operating curve was generated for IL-6 and MODS development with an IL-6 level of 350 pg/ml having the highest sensitivity and specificity within the developmental cohort. IL-6 was associated with MODS after adjusting for APACHE II, ISS, male gender and blood transfusions with an odds ratio of 3.9 [95% CI: 1.33–11.19]. An IL-6 level greater than 350 pg/ml within the validation cohort was associated with an increase in MODS score, MODS development, ventilator days, ICU length of stay (LOS), and hospital LOS. However, this IL-6 level was not associated with either the development of nosocomial infection or mortality. Conclusion Elevation in plasma IL-6 appears to correlate with a poor prognosis. This measurement may be useful as a biomarker for prognosis and serve to identify patients at higher risk of adverse outcome that would benefit from novel therapeutic interventions.

Predictive value of cytokines for developing complications after polytrauma

“…IL-6: (1) ARDS; two studies [37,45] could not relate ARDS to IL-6 concentration alterations, whereas two other studies [48,51] found a positive correlation (Table 2); (2) Sepsis; five studies [35,41,46,47,53] found an increased IL-6 production to be predictive for the development of sepsis, whereas five other studies [28,29,38,39,55] did not (Table 3); (3) MODS; all five prospective cohort studies [3,28,34,46,51] concluded that IL-6 is markedly increased in the early development of MODS ( Dekker ABE et al . Do cytokines predict polytrauma outcome IL-10: (1) Three studies, two prospective [54,57] and one retrospective [14] , could not relate the serum IL-10 concentrations to the development of ARDS.…”

“…Cook et al [58] 2013 P-cc 83 (18) G-CSF 7% 7% 4 Cuschieri et al [34] 2010 P-coh 152 IL-6 37% 5% 5 Donnelly et al [37] 1994 P-coh 15 IL-6, -8, -1β; TNF- 49% 33%…”

“…Cuschieri et al [34] 2010 P-coh 152 29 (37%) > 350 pg/mL: Sensitivity 79%, specificity 76%; OR = 3.87 (95%CI: 1. Haasper et al [28] 2010 P-coh 94 21 (22%) Y [IL-6] is significantly higher in MODS on days 1 + 7 Oberholzer et al [46] 2000 P-coh 1276 516 (40%) Y [IL-6] is significantly higher in (severe) MODS Sousa et al [51] 2015 P-coh 99 34 (34%) > 294 pg/mL: AUC ROC 0.769 (95%CI: 0.414-0.736) Y [IL-6] > 294 pg/mL is associated with MODS at 48 + 72 h post injury IL- 8 Frink et al [3] 2009 P-coh 143 24 (17%) r = 0.53; sensitivity 0% N [IL-8] is significantly higher in MODS; does not predict development of MODS IL- 10 Frink et al [3] 2009 P-coh 143 24 (17%) r = 0.31; sensitivity 0% N [IL-10] is significantly higher in MODS; does not predict development of MODS Neidhardt et al [54] 1997 P-cc 417 92 (22%) Y [IL-10] is significantly higher in MODS on days 1 + 3 + 5 + 7 + 10 + 14 + 21 post injury Spielmann et al [57] 2001 P-cc 47 24 (51%) N [IL-10] is not related to the development of MODS Sousa et al [51] Frink et al [3] 2009 P-coh 143 24 (17%) r = 0.32; sensitivity 0% N [TNF-a] is significantly higher in MODS; does not predict development of MODS Hayakawa et al [31] 2010 P-coh 45 24 (53%) Y [TNF-a] is significantly higher in MODS on days 3 + 5 Sousa et al [51] 2015 P-coh 99 34 (34%) Y [TNF-a] is associated with MODS at 48 h post injury Spielmann et al [57] 2001 P-cc 47 24 (51%) N [TNF-a) is not associated with MODS IL-1β…”

“…Paunel-Görgülü et al [47] 2011 P-coh 47 (17) IL-6 38% 11% 34 Raymondos et al [48] 2012 P-coh 24 IL-6, -8, -1β, TNF- 29% 4% 35 Roetman et al [60] 2008 P-cc 229 (110) IL-18, -4; IFN-γ 16% 36 Schinkel et al [61] 2005 P-cc 216 (110) IL-11 4% 16% 37 Sherry et al [14] 1996 R-cc 66 (10) IL-10 8% 39% 2% 38 Sousa et al [51] 2015 P-coh 99 IL-6, -10; TNF- 19% 34% 28% 38 Spielmann et al [57] 2001 P-cc 47 (15) TNF- 11% 30% 51% 23% 39 Svoboda et al [62] 1994 P-cc 42 (12) IL-1β, -2, -6; TNF- 33% 26% 40 Wick et al [49] 2000 P-coh 37 IL-12 11% 16% 41 Yagmur et al [63] 2005 P-cc 99 (10) IL-1, -2, -6, -8; TNF- 17% Table 1 Overview of included studies, the studied cytokines and the outcome parameters (acute respiratory distress syndrome, sepsis, muli-organ dysfunction syndrome, multi-organ failure, mortality)…”

Perbedaan Kadar IL-6 dan C-Reactive Protein pada Anak Pascabedah Perut dengan Bedah Saraf

“…Kadar Il-6 ≥350 pg/mL dalam 12 jam pasca injury merupakan prediktor disfungsi multi organ (MODS). 9 Tidak didapatkan perbedaan median kadar IL-6 hari pertama dan ke-5 pascabedah pada kedua kelompok jenis operasi. Hal tersebut memberikan gambaran bahwa bedah saraf dan bedah perut memiliki derajat kerusakan jaringan yang sama.…”