A Cyanobacterial Lipopolysaccharide Antagonist Inhibits Cytokine Production Induced byNeisseria meningitidisin a Human Whole-Blood Model of Septicemia

Abstract

Septicemia caused by Neisseria meningitidis is characterized by increasing levels of meningococcal lipopolysaccharide (Nm-LPS) and cytokine production in the blood. We have used an in vitro human whole-blood model of meningococcal septicemia to investigate the potential of CyP, a selective Toll-like receptor 4 (TLR4)-MD-2 antagonist derived from the cyanobacterium Oscillatoria planktothrix FP1, for reducing LPS-mediated cytokine production. CyP (>1 g/ml) inhibited the secretion of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1␤ (IL-1␤), and IL-6 (by >90%) and chemokines IL-8 and monocyte chemoattractant protein 1 (by ϳ50%) induced by the treatment of blood with pure Nm-LPS, by isolated outer membranes, and after infection with live meningococci of different serogroups. In vitro studies with human dendritic cells and TLR4-transfected Jurkat cells demonstrated that CyP competitively inhibited Nm-LPS interactions with TLR4 and subsequent NF-B activation. These data demonstrate that CyP is a potent antagonist of meningococcal LPS and could be considered a new adjunctive therapy for treating septicemia.

Neuroprotective Effects of Toll-Like Receptor 4 Antagonism in Spinal Cord Cultures and in a Mouse Model of Motor Neuron Degeneration

“…An LPS-like molecule extracted from the cyanobacterium Oscillatoria Planktothrix FP1 (CyP) dose-dependently inhibited TLR4-mediated inflammatory effects in vitro (32,33) and in vivo in a model of lethal endotoxin shock (32). TLR4 inhibition by CyP had an anticonvulsant effect on kainate-induced seizures in mice (44).…”

“…by TRI reagent (SigmaAldrich), as described previously (32,33). The product was treated with DNase (20 μg/mL) and RNase (10 μg/ mL) in 50 mmol/L Tris, 10 mmol/L MgCl 2 , pH 7.5, for 2 h at room temperature before addition of proteinase K (100 μg/mL) and incubation overnight at 37°C.…”

Host response toCandida albicansbloodstream infection and sepsis

“…[43][44][45][46] With regard to activation of host immunity, whole blood infection assays can provide time-resolved data on cell activation, localization and physiological state of the pathogen. Most importantly whole blood infection assays require minimal pre-analytical handling of the cells.…”

Albumin lavage does not improve the outcome of meconium aspiration syndrome

“…Suction of the trachea and oropharynx at delivery decreased the incidence of mild and moderate MAS (8;9). MAS is no longer considered to be a postnatal disorder caused by postnatal aspiration, but rather a disorder with antepartum, intrapartum and neonatal causes (10). Now, the hypothesis is that aspiration of meconium may occur in utero, during or after delivery, and that a chronic in utero insult may be responsible for severe MAS (11;12).…”