IntroductionGelsolin is an actin-binding plasma protein that is part of an 'actin-scavenging' system. Studies suggest that plasma gelsolin may play a crucial role in the pathophysiology of sepsis. Little is known about the course of plasma gelsolin levels over time in patients with severe sepsis. The aim of the study was to investigate plasma gelsolin levels in severe septic patients and to determine whether these levels predict the severity or clinical outcome of severe sepsis.MethodsNinety-one patients who were diagnosed with severe sepsis at admission to a surgical intensive care unit were enrolled, and admission plasma gelsolin levels were recorded. Plasma gelsolin levels were recorded daily in 23 of these patients. Daily plasma gelsolin levels were recorded in an additional 15 nonseptic critically ill patients. Fifteen volunteers served as healthy control individuals. Plasma gelsolin levels were measured using an enzyme-linked immunosorbent assay. Concentrations of IL-6, IL-10 and tumour necrosis factor (TNF)-α were also measured on intensive care unit admission.ResultsThe admission gelsolin levels were significantly decreased in severe sepsis (20.6 ± 11.7 mg/l) compared with nonseptic critically ill patients (52.3 ± 20.3 mg/l; P < 0.001) and healthy control individuals (126.8 ± 32.0 mg/l; P < 0.001). Severe septic patients had increased IL-6 levels compared with nonseptic critically ill patients (20.0 ± 10.7 pg/ml versus 11.4 ± 13.9 pg/ml; P = 0.048), whereas no significant difference in IL-10 or TNF-α levels was observed (IL-10: 97.9 ± 181.5 pg/ml versus 47.4 ± 91.5 pg/ml, respectively [P = 0.425]; TNF-α: 14.2 ± 13.9 pg/ml versus 6.9 ± 5.3 pg/ml, respectively; P = 0.132). Survivors of severe sepsis exhibited substantial recovery of their depressed plasma gelsolin levels, whereas gelsolin levels in nonsurvivors remained at or below their depleted admission levels.ConclusionPlasma gelsolin may be a valuable marker for severe sepsis. Recovery of depleted plasma gelsolin levels correlated with clinical improvement. The prognostic role of plasma gelsolin in critical illness requires further investigation in a large cohort.

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays an important role in a variety of diseases. However, the role of NLRP3 in the human intervertebral disc (IVD) degeneration remains unknown. In the present study, we assessed the expression levels of the NLRP3 inflammasome and its downstream targets caspase-1 and IL-1b in 45 degenerate and seven nondegenerate IVD samples. The correlation between the degeneration scores and expression levels of NLRP3, caspase-1, and IL-1b were also analyzed. The mRNA expression levels of the three molecules (NLRP3, caspase-1, and IL-1b) were higher in the degenerate IVDs group than the controls (nondegenerate IVDs group). Immunohistochemistry showed that the expression levels of all three molecules were markedly increased in the nucleus pulposus of degenerate IVDs compared with nondegenerate IVDs. There was a positive correlation between the degeneration scores and the expression levels of the NLRP3 inflammasome as well as its downstream targets caspase-1 and IL-1b. The findings suggest that excessive activation of the NLRP3 inflammasome results in overproduction of downstream IL-1b, which participates in the pathogenesis of human IVD degeneration. Therefore, the NLRP3 inflammasome might serve as a potential therapeutic target for the prevention and treatment of IVD degeneration. Anat Rec,