Inhibition of the cannabinoid 2 receptor in CNS-injury induced immunodeficiency syndrome.
Central nervous system (CNS) injury is classified as an independent factor, increasing patients' susceptibility to infections. The concept of infection susceptibility and impaired immune function is referred to as CNS-injury induced immunodeficiency syndrome (CIDS). The endocannabinoid system, an important homeostatic system that can modulate immune function, contributes to the consequences of an acute CNS injury. The actions of the endocannabinoid system are mediated via cannabinoid receptors, cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R), the latter of which are highly expressed by immune cells and upregulated as a result of infectious and non-infectious stressors. While the role of the CB2R in CNS immunity is primarily anti-inflammatory, focusing on the inhibition of the CB2R pathways may be of benefit for therapeutic targeting of the immunosuppression in CIDS. We hypothesize that inhibition of the CB2R will result in a decrease in the immunosuppression seen in CIDS, providing the patient protection against common infections such as pneumonia and urinary tract infections. However, due to the high variability of the patients' immune status during and after an acute CNS injury, identifying the most effective therapeutic window and CB2R antagonist dosage for effective immunostimulation is pivotal.
Department of Anaesthesia, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: chlehmann@dal.ca.
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Lehmann
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
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Burkovskiy
Department of Surgery, University of Cincinnati, OH, USA.
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Kuethe
Department of Anaesthesia, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
J
J
Zhou
Department of Surgery, University of Cincinnati, OH, USA.
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Caldwell
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
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Kelly
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy*; D002490:Central Nervous System / Q000276:immunology / Q000293:injuries*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D018448:Models, Immunological; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000276:immunology / Q000473:pathology*
C588309:CNR2 protein, human; D043885:Receptor, Cannabinoid, CB2