Shock. 2022 Nov 28. doi: 10.1097/SHK.0000000000002051. Online ahead of print.
ABSTRACT
BACKGROUND: Interleukin (IL)-6 is a multifunctional cytokine with both a pro- and anti-inflammatory role. In many studies, IL-6 increases rapidly after burn injury and is associated with poor outcomes. However, there are two aspects to IL-6; it can signal via its soluble IL-6 Receptor (sIL-6R), which is referred to as trans-signalling and is regarded as the proinflammatory pathway. The role of sIL-6R post-burn injury has yet to be explored in its entirety. We hypothesized that patients with a lower ratio of IL-6 to sIL-6R would have worse outcomes.
METHODS: Patients admitted to our burn centre within seven days of injury were included in this study. Patients were divided into two groups based on IL-6 and sIL-6R levels measured within the first seven days post-burn injury. Patients were in the high ratio group if their IL-6:sIL-6R ratio was ≥0.185. Clinical outcomes included organ biomarkers, morbidities, and hospital length of stay. Groups were compared using Student’s t-test, Mann-Whitney U, and Fisher’s exact test as appropriate; a P value of <0.05 was considered statistically significant.
RESULTS: We studied 86 patients with a median age of 50 (36 – 66) and a median total body surface area (TBSA) burn of 18% (10 – 31). There were 40 patients categorized with a low IL-6:sIL-6R ratio and 46 patients with a high IL-6:sIL-6R ratio. Patients in the high IL-6:sIL-6R ratio group had a significantly greater TBSA burn (p < 0.001) and a significantly greater proportion of patients with inhalation injury (p = 0.001). Levels of IL-6 were significantly higher in patients with a high IL-6:sIL-6R ratio (p < 0.0001). However, levels of sIL-6R were not significantly different among the low and high groups (p = 0.965). Mortality was significantly greater in the high IL-6:sIL-6R ratio group (3% vs. 26%; p = 0.002).
CONCLUSIONS: Interestingly, patients with a higher ratio of IL-6:sIL-6R had significantly greater mortality. Using sIL-6R as a marker for the proinflammatory immune response, we expected patients with a lower IL-6:sIL-6R ratio to have poor outcomes, typically associated with a hyperinflammatory or exaggerated immune response. However, the absolute value of sIL-6R did not differ. This suggests that classical signalling of IL-6 via its membrane-bound receptor, with an anti-inflammatory function, is essential.
PMID:36427079 | DOI:10.1097/SHK.0000000000002051
