Delta-9-Tetrahydrocannabinol Decreases Host Resistance to Herpes Simplex Virus Type 2 Vaginal Infection in the B6C3F1 Mouse

Mishkin, Eric M.; Cabral, Guy A.

doi:10.1099/0022-1317-66-12-2539

Cited by 53 publications

(23 citation statements)

References 13 publications

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“…During HIV infection, there is a reduction in CD4+ T cells and IFN-γ concentration [69]. During SIV infection, the activity of NK cells is inhibited [68], resulting in increased host mortality [63,65,66], and, in an influenza virus infection, the viral load is also increased [77]. In the studies in vitro, different cannabinoids increased HCV [59] and HSV replication [60,61].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, THC has been found to inhibit macrophage-extrinsic anti-HSV activity [64]. Experiments in vivo, using mice and guinea pigs, reported that THC decreased host resistance to HSV-2 vaginal infection, as observed by: (1) the greater frequency and severity of genital lesions, (2) higher mortality, and (3) higher virus titers in vaginal secretions and reduced IFN titers [63,65,66], indicating that cannabinoids induce a decreased resistance to HSV-2 ( Table 2).…”

Section: Herpesmentioning

confidence: 99%

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Immunoregulatory Role of Cannabinoids during Infectious Disease

Hernández-Cervantes

Méndez-Dı́az²,

Prospéro-Garcı́a³

et al. 2017

Neuroimmunomodulation

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Although the endocannabinoid system (ECS) is involved in the regulation of several physiological processes, including sleep and the immune response, its role during infections has not been fully studied. It is well known that the use of this drug increases susceptibility to infections because of the impact on the modulation of the immune system. Concerning the medicinal or recreational use of marijuana, its influence on the course of an infection, whether this has been caused by bacteria, viruses, parasites, and to a lesser degree, fungi, has been reported. Furthermore, there is evidence suggesting the involvement of the ECS in the control and elimination of infectious agents such as bacteria, viruses, and some protozoa; in the case of fungi, few studies are available so far. The purpose of this review is to present the existing studies related to infections and the ECS, the microbicidal effects of compounds isolated from Cannabis sativa, and the association between marijuana use and the development of rare pathologies in specific diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Herpesmentioning

confidence: 99%

Immunoregulatory Role of Cannabinoids during Infectious Disease

Hernández-Cervantes

Méndez-Dı́az²,

Prospéro-Garcı́a³

et al. 2017

Neuroimmunomodulation

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“…Experimental animal studies have also suggested that THC treatment causes increased susceptibility to various infectious agents (Table 4). Disease progression and mortality in different animal models were increased on infection with herpes simplex virus (HSV) and Friend leukemia virus (FLV) (35,147,222) and with bacterial pathogens such as Listeria, Treponema, and Staphylococcus (87,149,170).…”

Section: Marijuana-induced Enhancement Of Susceptibility To Infectionmentioning

confidence: 99%

Microbial Infections, Immunomodulation, and Drugs of Abuse

2003

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The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS

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“…One of the main bioactive ingredients of cannabis, THC was previously shown to increase the susceptibility of mice to bacterial, protozoan, and viral infections [14][15][16][17]. This effect of THC is linked to CB 2 receptor activation, decreased phagocytosis by macrophages, downregulation of proinflammatory cytokine production, and the polarization of T cells toward a Th2 phenotype [18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

2-Arachidonoyl-glycerol- and arachidonic acid-stimulated neutrophils release antimicrobial effectors against E. coli, S. aureus, HSV-1, and RSV

Chouinard

Turcotte

Guan

et al. 2013

Journal of Leukocyte Biology

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The endocannabinoid 2-AG is highly susceptible to its hydrolysis into AA, which activates neutrophils through de novo LTB 4 biosynthesis, independently of CB activation. In this study, we show that 2-AG and AA stimulate neutrophils to release antimicrobial effectors. Supernatants of neutrophils activated with nanomolar concentrations of 2-AG and AA indeed inhibited the infectivity of HSV-1 and RSV. Additionally, the supernatants of 2-AG-and AA-stimulated neutrophils strongly impaired the growth of Escherichia coli and Staphylococcus aureus. This correlated with the release of a large amount (micrograms) of α-defensins, as well as a limited amount (nanograms) of LL-37. All the effects of AA and 2-AG mentioned above were prevented by inhibiting LTB 4 biosynthesis or by blocking BLT 1 . Importantly, neither CB 2 receptor agonists nor antagonists could mimic nor prevent the effects of 2-AG, respectively. In fact, qPCR data show that contaminating eosinophils express ~100-fold more CB 2 receptor mRNA than purified neutrophils, suggesting that CB 2 receptor expression by human neutrophils is limited and that contaminating eosinophils are likely responsible for the previously documented CB 2 expression by freshly isolated human neutrophils. The rapid conversion of 2-AG to AA and their subsequent metabolism into LTB 4 promote 2-AG and AA as multifunctional activators of neutrophils, mainly exerting their effects by activating the BLT 1 . Considering that nanomolar concentrations of AA or 2-AG were sufficient to impair viral infectivity, this suggests potential physiological roles for 2-AG and AA as regulators of host defense in vivo.

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Delta-9-Tetrahydrocannabinol Decreases Host Resistance to Herpes Simplex Virus Type 2 Vaginal Infection in the B6C3F1 Mouse

Cited by 53 publications

References 13 publications

Immunoregulatory Role of Cannabinoids during Infectious Disease

Immunoregulatory Role of Cannabinoids during Infectious Disease

Microbial Infections, Immunomodulation, and Drugs of Abuse

2-Arachidonoyl-glycerol- and arachidonic acid-stimulated neutrophils release antimicrobial effectors against E. coli, S. aureus, HSV-1, and RSV

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