Abstract
The endocannabinoid system (ECS) is involved in many physiological processes and has been suggested to play a critical role in the immune response and the central nervous system (CNS). Therefore, ECS modulation has potential therapeutic effects on immune dysfunctional disorders, such as sepsis and CNS injury-induced immunodeficiency syndrome (CIDS). In sepsis, excessive release of pro- and anti-inflammatory mediators results in multi-organ dysfunction, failure, and death. In CIDS, an acute CNS injury dysregulates a normally well-balanced interplay between CNS and the immune system, leading to increased patients’ susceptibility to infections. In this review, we will discuss potential therapeutic modulation of the immune response in sepsis and CNS injury by manipulation of the ECS representing a novel target for immunotherapy.
Highlights
The endocannabinoid system (ECS) is involved in many physiological processes including metabolism, inflammation, pain, and neurotransmission (De Petrocellis and Di Marzo, 2009; Pandey et al, 2009)
We suggest that the common mechanism for modulating and controlling the response of the immune system can be achieved through delicate interplay between the endocannabinoid, central nervous and immune systems
We have demonstrated inhibition of CB2R by the selective antagonist, AM 630, significantly increased immune function as indicated by an increased leukocyte adherence to endothelia in animals challenged with LPS after hypoxia-ischemia (HI)-induced central nervous system (CNS) injury
Summary
The endocannabinoid system (ECS) is involved in many physiological processes including metabolism, inflammation, pain, and neurotransmission (De Petrocellis and Di Marzo, 2009; Pandey et al, 2009) It consists of endogenous cannabinoids (EC), cannabinoid receptors (CBR), and EC metabolizing enzymes (De Petrocellis and Di Marzo, 2009; Pertwee et al, 2010). CB2R are primarily expressed on immune cells but are identified in selected CNS areas and some peripheral tissues (Klein, 2005) Another G protein-coupled receptor, GPR55, has garnered much attention due to its activation by EC and its impact on the immune system (Pertwee, 2007; Yang et al, 2016a). We will focus on modulation of CB2 and GPR55 receptors on immune response in two inflammatory disorders, sepsis, and CNS injury. We suggest that the common mechanism for modulating and controlling the response of the immune system can be achieved through delicate interplay between the endocannabinoid, central nervous and immune systems
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