The intracerebroventricular injection of rimonabant inhibits systemic lipopolysaccharide-induced lung inflammation

Abstract

We investigated the role of intracerebroventricular (ICV) injection of rimonabant (500 ng), a CB1 antagonist, on lipopolysaccharide ((LPS) 5mg/kg)-induced pulmonary inflammation in rats in an isolated perfused lung model. There were decreases in pulmonary capillary pressure (Ppc) and increases in the ((Wet-Dry)/Dry lung weight)/(Ppc) ratio in the ICV-vehicle/LPS group at 4 hours. There were decreases in TLR4 pathway markers, such as interleukin receptor-associated kinase-1, IκBα, Raf1 and phospho-SFK(Tyr416) at 30min and at 4hr increases in IL-6, vascular cell adhesion molecule-1 and myeloperoxidase in lung homogenate. Intracerebroventricular rimonabant attenuated these LPS-induced responses, indicating that ICV rimonabant modulates LPS-initiated pulmonary inflammation.

Dual inhibition of CB1 receptors and iNOS, as a potential novel approach to the pharmacological management of acute and long COVID‐19

“…In turn, CB 1 receptor blockade has been shown to exert anti‐viral effects by repressing viral replication and to protect from or reverse sepsis (Shahidi et al, 2014; Singh et al, 2018). Activation of peripheral CB 1 receptors also contributes to septic hypotension whereas CB 1 receptor blockade protects against endotoxin‐induced hypotension (Batkai et al, 2001; Varga et al, 1998) and lung injury (Johnson et al, 2015). Additionally, CB 1 receptor up‐regulation by potent synthetic cannabinoids is directly linked to hypoxia and acidosis leading to ARDS and respiratory failure (Alon & Saint‐Fleur, 2017).…”

Possible Role of Adipose Tissue and the Endocannabinoid System in Coronavirus Disease 2019 Pathogenesis: Can Rimonabant Return?

“…The interaction of rimonabant with CB1 adipocytes is thus expected to decrease the inflammatory state of abdominal tissue, in a manner similar to the specific invalidation of CB1 in adipocytes (11). In addition, CB1 blockade was shown to reduce pulmonary inflammation in at least two different preclinical models (12,13). This might be particularly relevant in the context of COVID‐19, although the opposite was observed in mice infected with respiratory syncytial virus (14).…”