Sirtuin 2 expression levels may predict the progression of sepsis survivors to chronic critical illness

BACKGROUND: Sirtuin 2 (SIRT2) is a conserved deacetylase that participates in the regulation of inflammation in sepsis. In this observational prospective study, we investigated the predictive value of the SIRT2 expression level in the development of chronic critical illness (CCI) in patients with sepsis. METHODS: A total of 128 critically ill patients with sepsis or septic shock were enrolled and assigned to the CCI group, rapid recovery (RAP) group, or early death group according to their clinical trajectories. Patients’ demographic and clinical information, as well as laboratory data, including C-reactive protein (CRP) level and total lymphocyte counts, were collected. Blood samples were obtained at admission and on days 1, 4, 7, 10, 14, and 21 (days 14 and 21 for the CCI group only). Peripheral blood mononuclear cells were isolated, and SIRT2 expression was measured by real-time polymerase chain reaction. Serum levels of interleukin (IL)-6 and IL-10 were measured by enzyme-linked immunosorbent assay. RESULTS: Our cohort included 37 CCI and 82 RAP patients, and 9 early death patients, who died within 14 days of intensive care unit (ICU) admission. Compared with the RAP group, CCI patients showed elevated CRP and IL-6 levels throughout the observation period, reflecting a sustained inflammatory response. However, decreases in total lymphocyte count and IL-10 expression in these patients were indicative of immunosuppression. SIRT2 mRNA level was lower in CCI and RAP patients compared with healthy controls at the initial stage of hospitalization, but increased starting on day 4 and continued to increase for the duration of hospitalization. By day 10, SIRT2 expression had almost returned to normal in RAP patients; however, in CCI patients, it continued to increase until the end of the observation period. A receiver-operating characteristic curve analysis showed that the expression level of SIRT2 at 10 days predicts the occurrence of CCI (P<0.05). CONCLUSIONS: SIRT2 expression may be a useful marker for identifying sepsis survivors who are at risk of progressing to CCI.