Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock

Abstract

Sepsis is a potentially life-threatening complication of an infection. Sepsis is mostly the consequence of systemic bacterial infections leading to exacerbated activation of immune cells by bacterial products, resulting in enhanced release of inflammatory mediators. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a critical factor in the pathogenesis of sepsis, which is sensed by Toll-like receptor 4 (TLR4). The scientific community highly pursues the development of antagonists capable of blocking the cytokine storm by blocking TLR4. We report here that a recombinant molecule of 14.5 kDa belonging to the Fasciola hepatica fatty acid binding protein (Fh15) is capable of significantly suppressing the LPS-induced cytokine storm in a mouse model of septic shock when administered by the intraperitoneal route 1 h after a lethal LPS injection. These results suggest that Fh15 is an excellent candidate for drug development against endotoxemia.

Potential Influence of Helminth Molecules on COVID-19 Pathology

“…Specifically, the helminth parasite Fasciola hepatica has shown immunomodulatory properties, and several molecules from this parasite have been described as potent immunomodulators [7]. Derivatives of these molecules in their synthetic, safe formats have given rise to promising results; for example, a 68 mer peptide of helminth defense molecule (HDM) has been shown to inhibit inflammation and airway hyper-reactivity in murine experimental asthma [8], and the fatty-acid-binding recombinant protein Fh15 blocked the lipopolysaccharide (LPS)-induced cytokine storm in a murine model [9]. As a result, recombinant safeto-use forms of the above-mentioned molecules are available.…”

Naltrexone a potential therapeutic candidate for COVID-19

“…Peripheral blood of severe COVID-19 patients has also shown a high level of cytokine storm (Wu and Yang, 2020 ). Keeping in mind the ability of lipopolysaccharide (LPS) to cause sepsis and triggers an uncontrolled systemic inflammatory response in murine macrophage cells (Ramos-Benitez et al., 2018 ), we treated macrophage cells with LPS (1 µg/ml) in the presence and absence of LDN (5 µM). The dose of LDN chosen is non-toxic ( Figure S2 ) as found in cell viability using MTT (4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay following the standard protocol (Dogra et al., 2019 ).…”

Naltrexone a potential therapeutic candidate for COVID-19

“…Peripheral blood of severe COVID-19 patients has also shown a high level of cytokine storm 14 . Keeping in mind the ability of lipopolysaccharide (LPS) to cause sepsis and triggers an uncontrolled systemic inflammatory response in murine macrophage cells 15 , we treated macrophage cells with LPS (1μg/ml) in presence and absence of LDN (5 μM). Results demonstrated that LPS treatment significantly induced expression on pro-inflammatory cytokines (IL-1β, IL-6and TNF-a) whereas, LDN significantly inhibited LPS expression of IL-1β, IL-6and TNF-a in macrophage cells (Fig.…”