Time course of plasma gelsolin concentrations during severe sepsis in critically ill surgical patients

Abstract

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.

Plasma Gelsolin Promotes Proliferation of Mesangial Cell in IgA Nephropathy

“…In particular, pGSN is secreted into extracellular fluids. Serum pGSN levels decrease markedly in a variety of clinical conditions, such as lung injury [17], hepatitis B-associated liver cirrhosis [18], sepsis [19], major trauma [20], brain injury [21,22], certain cancers [23,24], Alzheimer's disease [25], rheumatoid arthritis [11] and multiple sclerosis [26]. Furthermore, certain studies have demonstrated that GSN is up-regulated in patients with idiopathic pulmonary fibrosis (IPF) or fibrotic nonspecific interstitial pneumonia [27,28].…”

Behind the scenes of vitamin D binding protein: More than vitamin D binding

“…Liver (parenchymal as well as nonparenchymal cells), lungs and spleen are responsible for the uptake of G-actin-DBP complexes by plasma membrane receptors [76]. Multiple studies have illustrated the important role of the actin scavenging system during severe sepsis [28,77], liver diseases [78,79], respiratory failure [80], preeclampsia [81,82], cardiac surgery [83] and after burn injuries [84].…”

Visual Insight into How Low pH Alone Can Induce Actin-severing Ability in Gelsolin under Calcium-free Conditions

“…That way, it protects essential organs from otherwise toxic F-actin, whose release goes up substantially during injury (6). Importantly, depleted levels of plasma gelsolin were found in many intensive care patients (7), and administration of exogenous gelsolin in mouse models of burn and sepsis showed a remarkable rate of recovery relative to placebo, promoting the concept of "gelsolin replacement therapy" (8). The existing understanding is that to stimulate its actin modulation functions, gelsolin primarily binds to Ca 2ϩ ions and gets activated, or in other words, undergoes shape changes that make it actin binding-competent (2,4).…”