Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis

• Published in: Journal of neuroimmunology Vol. 303; pp. 66 - 74
• Main Authors: Annunziata, Pasquale, Cioni, Chiara, Mugnaini, Claudia, Corelli, Federico
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2017
• Subjects: Adamantane - analogs & derivatives; Adamantane - pharmacology; Adamantane - therapeutic use; Adult; Allergy and Immunology; Cannabinoid Receptor Agonists - pharmacology; Cannabinoid Receptor Agonists - therapeutic use; Cannabinoids; CB2 receptor; Cells, Cultured; Cytokines - immunology; Cytokines - metabolism; Female; Humans; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Multiple Sclerosis - metabolism; Neuroimmunomodulation; Neuroinflammation; Neurology; Quinolones - pharmacology; Quinolones - therapeutic use; Receptor, Cannabinoid, CB2 - agonists; Receptor, Cannabinoid, CB2 - immunology; Receptor, Cannabinoid, CB2 - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; CB2 receptor; Neuroinflammation; Cannabinoids; Multiple sclerosis; Neuroimmunomodulation
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2016.12.009

COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects and patients with relapsing-remitting multiple sclerosis (MS). In MS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanism involving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines. COR167 was also able to reduce in vitro migration of stimulated immunocompetent cells through human brain endothelium associated with a significant reduction of levels of several chemokines. These findings demonstrate that COR167 exerts potent immunomodulatory effects and confirm the cannabinoid CB2 receptor as a novel pharmacological target to counteract neuroinflammation. [Display omitted] •COR167 inhibits proliferation of normal and MS immune cells.•COR167 shifts Th1 towards Th2 phenotype and down-regulates IL-4, IL-5 and Th17 phenotype.•COR167 reduces in vitro cell trafficking through human brain endothelium.•Cannabinoid CB2 receptor is a pharmacological target to counteract neuroinflammation.