RESUMO
BACKGROUND: High mobility group box 1 (HMGB1) has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin (TM) seems to decrease HMGB1 activity. AIM: To investigate the role of the thrombomodulin/high mobility group box 1 (T/H) ratio in patients with sepsis and their association with their clinic, testing the hypothesis that higher ratios are associated with better outcomes. METHODS: Twenty patients diagnosed with sepsis or septic shock, according to the 2016 criteria sepsis and septic shock (Sepsis-3), were studied. Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization (D28). The following clinical outcomes were observed: Sequential Organ Failure Assessment (SOFA) score; Need for mechanical pulmonary ventilation; Presence of septic shock; Occurrence of sepsis-induced coagulopathy; Need for renal replacement therapy (RRT); and Death. RESULTS: The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM: 76.41 ± 29.21 pg/mL vs 37.41 ± 22.55 pg/mL among those whose SOFA scores were less than 12 points, P = 0.003. The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points, P = 0.001. The T/H ratio was, on average, three times higher in patients in need of RRT (0.38 ± 0.14 vs 0.11 ± 0.09), P < 0.001. CONCLUSION: Higher serum levels of TM and, therefore, higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy, while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.
RESUMO
INTRODUCTION: Despite advances in treatment of diabetes mellitus, its prevalence continues to rise globally. Medications available are unable to control the vascular complications. Proposals for new therapeutic targets must take into account the hyperglycemia-induced signaling pathways that give rise to the inflammatory profile of the disease. AREAS COVERED: How high-mobility-group box-1 (HMGB1) protein, acting as an activator of Toll-like receptors (TLR) and receptors for advanced glycation end products (RAGE), creates a functional tripod that contributes to increased production of pro-inflammatory mediators, and sustains the chronic inflammatory state associated with diabetes. The interaction of TLR2 and TRL4 with host-derived ligands, which links diabetic complications with the innate immune response, and the activation of RAGE, which induces a cascade of metabolic responses, leading to the production and secretion of pro-inflammatory cytokines. EXPERT OPINION: Considering the involvement of the innate immune system, in association with the role of HMGB1 as an activator of TLR and RAGE, diabetes should be considered and treated as a metabolic and immunological disease, triggered by hyperglycemia. HMGB1 plays a central role in mediating injury and inflammation, and interactions involving HMGB1-TLR-RAGE constitute a tripod that trigger NF-κB activation. Blockade or downregulation of HMGB1, and/or control of the inflammatory tripod, represent a promising therapeutic approach for the treatment of diabetes.