Selenocompounds and Sepsis: Redox Bypass Hypothesis for Early Diagnosis and Treatment: Part A—Early Acute Phase of Sepsis: An Extraordinary Redox Situation (Leukocyte/Endothelium Interaction Leading to Endothelial Damage)

Abstract

Significance: Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die. Multiple attempts to control sepsis at an early stage have been unsuccessful.

Delayed increase of plasma selenoproteins and absence of side effect induced by infusion of pharmacological dose of sodium selenite in septic shock: Secondary analysis of a multicenter, randomized controlled trial

“…As constantly seen in septic shock patients, we observed a profound decrease of plasma Se concentration at inclusion, which is between half to three-quarter of the reference value [12,24,32,33,36,39]. In contrast with the absence of clinical effect, we observed a marked increase of plasma Se selenoprotein-P concentrations as well as GPX3 activity with Na 2 SeO 3 administration until day-4 that seemed to have no impact on plasma inflammatory markers and lipid peroxidation.…”

“…It remains to date without specific treatment, at the exception of low dose steroids [9,10]. At the early phase of sepsis, endothelial dysfunction is a major event [2,11,12]. This dysfunction is notably related to the neutrophil respiratory bursts [12][13][14][15][16].…”

“…At the early phase of sepsis, endothelial dysfunction is a major event [2,11,12]. This dysfunction is notably related to the neutrophil respiratory bursts [12][13][14][15][16]. The selenium (Se) is required for the vital antioxidant selenoenzymes under the form of selenocystein aminoacid [17,18].…”

Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease

“…The imbalance in trace element concentrations underlines the chronic inflammatory nature of RA and an elevation of pro-inflammatory cytokines, with IL-6 and IL-1ß likely taking center stage for the observed effects on the micronutrient status [140,141]. Notably, the interaction between Se deficiency and enhanced inflammation is not necessarily unidirectional and self-limiting, but rather constitutes a vicious cycle with self-amplifying characteristics, similar to the situation in sepsis [142]. The Se status is known to affect NF-kB activity, and a reduced Se status will cause an up-regulation of a whole set of inflammation-relevant genes [143].…”

“…In parallel, the specific Se transport via SELENOP to target tissues becomes disrupted, and a systemic Se deficit may develop, in particular when baseline Se status is already low [8]. Notably, declining Se status and increasing cytokine concentrations are closing a feed-forward regulation, i.e., a self-amplifying loop [129,142,158]. The clinical conditions causing a decline in Se status show a considerable overlap to potential triggers for AID development, and both processes may be causally linked, i.e., acute Se deficiency may constitute an as-yet poorly appreciated trigger for AID development (Table 1).…”