The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

Abstract

Endocannabinoid system consists of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. CB2, to a great extent, and CB1, to a lesser extent, are involved in regulating the immune response. They also regulate the inflammatory processes by inhibiting pro-inflammatory mediator release and immune cell proliferation. This review provides an overview on the role of the endocannabinoid system with a major focus on cannabinoid receptors in the pathogenesis and onset of inflammatory and autoimmune pediatric diseases, such as immune thrombocytopenia, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, obesity, neuroinflammatory diseases, and type 1 diabetes mellitus. These disorders have a high social impact and represent a burden for the healthcare system, hence the importance of individuating more innovative and effective treatments. The endocannabinoid system could address this need, representing a possible new diagnostic marker and therapeutic target.

Cannabidiol and Vitamin D3 Impact on Osteogenic Differentiation of Human Dental Mesenchymal Stem Cells

“…CB2 receptors present in osteoblasts, osteocytes, and osteoclasts [ 19 ] have a more intense expression than CB1 [ 22 , 23 ] and have also been mentioned to be expressed on bone marrow stem cells [ 20 ]. CB1 and CB2 are part of the endocannabinoid system along with their endogenous ligands and enzymes [ 24 ]. Tetrahydrocannabinol (THC) and CBD are two of the most used cannabinoid derivates in research.…”

Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases

“…CBR2 selective agonists have been shown to attenuate several autoimmune diseases in mice [ 87 ]. CBR2 inhibits immune cell activation and pro-inflammatory mediator release and is a possible target in treating diseases connected to these phenomena, mainly inflammatory and autoimmune diseases: juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, obesity and neuroinflammatory diseases [ 88 , 89 ]. For example, CBR2 agonist—JWH-015—was able to reduce obesity-associated inflammation in mice [ 90 ].…”

“…Cytokines can act as pro- or anti-inflammatory agents and cannabinoids are able to modulate their release. Production of pro-inflammatory cytokines can be reduced by cannabinoids (IL-6 by anandamide, IL-12 and IFN-γ (interferon γ) by THC and CBR1, CBR2 partial agonists) [ 89 ]. Pro-inflammatory IL-2 and IFN-γ promote the differentiation of T-helper (Th) cells towards the Th1 subtype, while IL-4 and IL-5 promote differentiation towards the Th2 subtype.…”

“…Periodontitis, a chronic bacterial-induced disease of the supporting structures of the teeth can be promoted by marijuana derived canabinnoids (CBD, CBN, and THC). Each of them is able to reduce IL-12 p40, IL-6, IL-8, and TNF release induced by oral pathogens ( Porphyromonas gingivalis, Filifactor alocis, or Treponema denticola) while enhancing the anti-inflammatory cytokine IL-10 [ 89 ]. On the other hand, efficient inhibition of LPS, TNF-α, IL-1β stimulated IL-6, and MCP-1 production by CB2R ligands in hPDLFs (human periodontal ligament fibroblasts) can be promising for periodontal therapy, novel drugs development in context of improving oral health [ 103 ].…”

Correction: Argenziano, M., et al. The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases. Int. J. Mol. Sci. 2019, 20, 5875

“…The authors wish to make the following corrections to this paper [1]: Due to a lapse, the Funding section of the original version of the manuscript did not report the funding received to publish it [1].…”