Effect of Cannabidiol (CBD) on Canine Inflammatory Response: An Ex Vivo Study on LPS Stimulated Whole Blood

Overview

Journal Vet Sci

Publisher MDPI

Specialty Veterinary Medicine

Date 2021 Sep 26

PMID 34564578

Citations 11

Authors

Enrico Gugliandolo

Patrizia Licata

Alessio Filippo Peritore

Rosalba Siracusa

Ramona DAmico

Marika Cordaro

Roberta Fusco

Daniela Impellizzeri

Rosanna Di Paola

Salvatore Cuzzocrea

Rosalia Crupi

Claudia Dina Interlandi

Affiliations

Soon will be listed here.

Abstract

The use of cannabidiol (CBD) for animal species is an area of growing interest, for example for its anti-inflammatory and immuno-modulating properties, even though all of its biological effects are still not fully understood, especially in veterinary medicine. Therefore, the aim of this study was to investigate the anti-inflammatory and immuno-modulating properties of CBD for the first time directly in canine inflammatory response. We used an ex vivo model of LPS-stimulated whole dog blood. We stimulated the whole blood from healthy dogs with LPS 100 ng/mL for 24 h in the presence or not of CBD 50 and 100 μg/mL. We observed a reduction in IL-6 and TNF-α production from the group treated with CBD, but non-altered IL-10 levels. Moreover, we also observed from the CBD-treated group a reduction in Nf-κB and COX-2 expression. In conclusion, we demonstrated for the first time the anti-inflammatory and immuno-modulating properties of CBD directly in dogs' immune cells, using a canine ex vivo inflammatory model. The results obtained from these studies encourage further studies to better understand the possible therapeutic role of CBD in veterinary medicine.

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References

Gamble L, Boesch J, Frye C, Schwark W, Mann S, Wolfe L . Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Front Vet Sci. 2018; 5:165. PMC: 6065210. DOI: 10.3389/fvets.2018.00165. View

Peyravian N, Deo S, Daunert S, Jimenez J . Cannabidiol as a Novel Therapeutic for Immune Modulation. Immunotargets Ther. 2020; 9:131-140. PMC: 7445536. DOI: 10.2147/ITT.S263690. View

Joffre J, Yeh C, Wong E, Thete M, Xu F, Zlatanova I . Activation of CBR Promotes Lipopolysaccharide-Induced IL-10 Secretion by Monocytic Myeloid-Derived Suppressive Cells and Reduces Acute Inflammation and Organ Injury. J Immunol. 2020; 204(12):3339-3350. PMC: 7276941. DOI: 10.4049/jimmunol.2000213. View

Atalay S, Jarocka-Karpowicz I, Skrzydlewska E . Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel). 2019; 9(1). PMC: 7023045. DOI: 10.3390/antiox9010021. View

Jaffey J, Amorim J, DeClue A . Effect of calcitriol on in vitro whole blood cytokine production in critically ill dogs. Vet J. 2018; 236:31-36. DOI: 10.1016/j.tvjl.2018.04.010. View

Fusco R, Siracusa R, Peritore A, Gugliandolo E, Genovese T, DAmico R . The Role of Cashew ( L.) Nuts on an Experimental Model of Painful Degenerative Joint Disease. Antioxidants (Basel). 2020; 9(6). PMC: 7346149. DOI: 10.3390/antiox9060511. View

Yu C, Rupasinghe H . Cannabidiol-based natural health products for companion animals: Recent advances in the management of anxiety, pain, and inflammation. Res Vet Sci. 2021; 140:38-46. DOI: 10.1016/j.rvsc.2021.08.001. View

McHugh D, Tanner C, Mechoulam R, Pertwee R, Ross R . Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2. Mol Pharmacol. 2007; 73(2):441-50. DOI: 10.1124/mol.107.041863. View

Spierenburg E, Portengen L, Smit L, Krop E, Hylkema M, Rijkers G . Stability of individual LPS-induced ex vivo cytokine release in a whole blood assay over a five-year interval. J Immunol Methods. 2018; 460:119-124. DOI: 10.1016/j.jim.2018.06.018. View

10.

Sarr O, Dyck D, Mutch D . [Letter to the Editor] Protein phosphorylation status is preserved following dual RNA and protein extraction using the Qiagen RNeasy Mini Kit. Biotechniques. 2016; 61(5):233-235. DOI: 10.2144/000114471. View

11.

McGeough M, Pena C, Mueller J, Pociask D, Broderick L, Hoffman H . Cutting edge: IL-6 is a marker of inflammation with no direct role in inflammasome-mediated mouse models. J Immunol. 2012; 189(6):2707-11. PMC: 3495128. DOI: 10.4049/jimmunol.1101737. View

12.

Angelone D, Wessels M, Coughlin M, Suter E, Valentini P, Kalish L . Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivo. Pediatr Res. 2006; 60(2):205-9. DOI: 10.1203/01.pdr.0000228319.10481.ea. View

13.

Di Paola R, Fusco R, Gugliandolo E, DAmico R, Campolo M, Latteri S . The Antioxidant Activity of Pistachios Reduces Cardiac Tissue Injury of Acute Ischemia/Reperfusion (I/R) in Diabetic Streptozotocin (STZ)-Induced Hyperglycaemic Rats. Front Pharmacol. 2018; 9:51. PMC: 5808141. DOI: 10.3389/fphar.2018.00051. View

14.

Verrico C, Wesson S, Konduri V, Hofferek C, Vazquez-Perez J, Blair E . A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain. 2020; 161(9):2191-2202. PMC: 7584779. DOI: 10.1097/j.pain.0000000000001896. View

15.

Vuolo F, Petronilho F, Sonai B, Ritter C, Hallak J, Zuardi A . Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediators Inflamm. 2015; 2015:538670. PMC: 4458548. DOI: 10.1155/2015/538670. View

16.

Pagano S, Coniglio M, Valenti C, Federici M, Lombardo G, Cianetti S . Biological effects of Cannabidiol on normal human healthy cell populations: Systematic review of the literature. Biomed Pharmacother. 2020; 132:110728. DOI: 10.1016/j.biopha.2020.110728. View

17.

Kaplan B, Springs A, Kaminski N . The profile of immune modulation by cannabidiol (CBD) involves deregulation of nuclear factor of activated T cells (NFAT). Biochem Pharmacol. 2008; 76(6):726-37. PMC: 2748879. DOI: 10.1016/j.bcp.2008.06.022. View

18.

Winger E, Reed J, Ashoush S, El-Toukhy T, Ahuja S, Taranissi M . Degree of TNF-α/IL-10 cytokine elevation correlates with IVF success rates in women undergoing treatment with Adalimumab (Humira) and IVIG. Am J Reprod Immunol. 2011; 65(6):610-8. DOI: 10.1111/j.1600-0897.2010.00946.x. View

19.

De Briyne N, Holmes D, Sandler I, Stiles E, Szymanski D, Moody S . Cannabis, Cannabidiol Oils and Tetrahydrocannabinol-What Do Veterinarians Need to Know?. Animals (Basel). 2021; 11(3). PMC: 8003882. DOI: 10.3390/ani11030892. View

20.

Lodzki M, Godin B, Rakou L, Mechoulam R, Gallily R, Touitou E . Cannabidiol-transdermal delivery and anti-inflammatory effect in a murine model. J Control Release. 2003; 93(3):377-87. DOI: 10.1016/j.jconrel.2003.09.001. View