Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. Lipopolysaccharide (LPS) is usually used intratracheally to induce ALI in mice. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (um-PEA) in mice subjected to LPS-induced ALI. Histopathological analysis reveals that um-PEA reduced alteration in lung after LPS intratracheal administration. Besides, um-PEA decreased wet/dry weight ratio and myeloperoxidase, a marker of neutrophils infiltration, macrophages and total immune cells number and mast cells degranulation in lung. Moreover, um-PEA could also decrease cytokines release of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and interleukin (IL)-18. Furthermore, um-PEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration. Our study suggested that um-PEA contrasted LPS-induced ALI, exerting its potential role as an adjuvant anti-inflammatory therapeutic for treating lung injury, maybe also by p38/NF-κB pathway.
Highlights
Acute lung injury (ALI) represents the most severe form of the viral infection sustained by coronavirus disease 2019 (COVID-19)
UmPEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration
IL-6 is mainly produced by the innate immune system and is one of the first cytokines released in the acute phase of acute respiratory distress syndrome (ARDS)/ALI, and is followed by increases in the expression of IL-1β, IL-8 and tumor necrosis factor (TNF)-α [39]
Summary
Acute lung injury (ALI) represents the most severe form of the viral infection sustained by coronavirus disease 2019 (COVID-19). In the pathogenesis of viral infections, among immune cells, mast cells (MCs) play an important role as inflammatory mediators Various pathogens, such as viruses, bind MCs through the toll-like receptor (TLR), a bond that activates cells by promoting their degranulation and the release of pro-inflammatory chemicals and cytokines. Recent studies have proposed um-PEA as a potential adjunct in therapy for COVID patients, thanks to its ability to modulate inflammation and neuroinflammation, both peripherally and centrally [24,25] These pleiotropic properties could be taken into consideration for the introduction of um-PEA in the COVID-19 multidrug regimen, avoiding an increase in the dosage of immunosuppressants by planning a synergistic therapy between um-PEA and the latter [26,27]. The mechanisms underlying ALI are still unclear, so in the present study, we used a model of intratracheally LPS-induced ALI to evaluate the effects of um-PEA 30 mg/kg on regulation of inflammatory process in acute lung disease
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