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Canna~Fangled Abstracts

Selective CB2 Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury

By December 12, 2022January 3rd, 2023No Comments

. 2022 Dec 13;23(24):15857.

doi: 10.3390/ijms232415857.

Stefan Hall 1 2, Sufyan Faridi 2, Purvi Trivedi 2 3, Saki Sultana 3 4, Bithika Ray 2, Tanya Myers 2, Irene Euodia 2, David Vlatten 2, Mathieu Castonguay 5, Juan Zhou 2 6, Melanie Kelly 2 3 4, Christian Lehmann 1 2 3 6
Affiliations 

Free PMC article

Abstract

Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB2) has been shown to reduce cytokine release in various in vivo and in vitro studies. Herein, we investigated the effect of HU-308, a specific CB2 agonist, on systemic and pulmonary inflammation in a model of pneumonia-induced ALI. C57Bl/6 mice received intranasal endotoxin or saline, followed by intravenous HU-308, dexamethasone, or vehicle. ALI was scored by histology and plasma levels of select inflammatory mediators were assessed by Luminex assay. Intravital microscopy (IVM) was performed to assess leukocyte adhesion and capillary perfusion in intestinal and pulmonary microcirculation. HU-308 and dexamethasone attenuated LPS-induced cytokine release and intestinal microcirculatory impairment. HU-308 modestly reduced ALI score, while dexamethasone abolished it. These results suggest administration of HU-308 can reduce systemic inflammation without suppressing pulmonary immune response in pneumonia-induced ALI and systemic inflammation.

Keywords: ARDS, acute lung injury, cannabinoid type II receptor (CB2), cytokines, inflammation, intravital microscopy, microcirculation

Conflict of interest statement

The authors declare no conflict of interest.

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Grant support

This work was supported in part through an unrestricted grant from Tetra Bio-Pharma Inc., Canada, and through the Legacy Research Fund from the Lung Association of Nova Scotia, Canada. S.H. would like to acknowledge funding through student research scholarships from the Anesthesia Research Fund, Department of Anesthesia, Pain Management and Perioperative Medicine, and the I3V Wave, Dalhousie University, Halifax, Nova Scotia, Canada.

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