Immune function alterations in mice tolerant to Δ9-tetrahydrocannabinol: functional and biochemical parameters

Massi, Paola; Sacerdote, Paola; Ponti, W.; Fuzio, Domenica; Manfredi, Barbara; Viganò, Daniela; Rubino, Tiziana; Bardotti, Massimiliano; Parolaro, Daniela

doi:10.1016/s0165-5728(98)00177-5

Cited by 40 publications

(27 citation statements)

References 26 publications

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“…During this period, mice received increasing s.c. doses of THC once a day (5 mg/kg pnd 80-82; 10 mg/kg pnd 83-85; 15 mg/kg pnd 86-89) or its vehicle. The dose protocol was chosen on the basis of previous experiments from our and other groups, and the dosage was increased over 10 days to counteract the possible development of tolerance, which has been previously observed for some immune responses (Massi et al 1998;Lombard et al 2011;Moretti et al 2014). Moreover, we have previously demonstrated that this dosage reached plasma concentrations in mice similar to those measured in human heavy marijuana smokers (Moretti et al 2014).…”

Section: Treatmentsmentioning

confidence: 99%

“…It is also well known that THC modulates immune responses, affecting both innate and acquired immunity (Cabral and Dove Pettit 1998;Massi et al 1998Massi et al , 2000Massi et al , 2006. THC exerts a significant anti-inflammatory and immunosuppressive effect in adults (Klein et al 2000;Newton et al 2009); this was a factor in the decision to legalize marijuana for medical purposes in several European Countries (Berdyshev 2000;Klein 2005;Mackie 2006;Pertwee 2009).…”

Section: Introductionmentioning

confidence: 99%

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Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages

Moretti

Franchi

Castelli

et al. 2015

J Neuroimmune Pharmacol

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Cannabis use is frequent among adolescents. Its main component, delta-9-tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood. The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male mice were used. Acute THC administration induced a similar reduction of macrophage proinflammatory cytokines and an IL-10 increase in adult and adolescent mice. THC did not affect brain cytokines in adult mice, but a proinflammatory cytokine decrease was evident in the adolescent brain. A similar effect was present in the hypothalamus and hippocampus after 10 days' THC administration. In contrast, when brain cytokines were measured 47 days after the final THC administration, we observed an inverted effect in adult mice treated as adolescents, i.e., IL-1β and TNF-α increased and IL-10 decreased, indicating a shift toward neuroinflammation. These data suggest that THC exposure in adolescence has long-lasting effects on brain cytokines that parallel those present in the periphery. This modulation may affect vulnerability to immune and behavioural diseases in adulthood.

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Section: Treatmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages

Moretti

Franchi

Castelli

et al. 2015

J Neuroimmune Pharmacol

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“…An indirect immunofluorescence technique, described earlier for phenotyping murine, bovine and feline leukocytes (Poli et al, 1996;Massi et al, 1998;Paltrinieri et al, 2003), was used to evaluate CD4, CD8, CD14 and CD4/CD8 ratios in the sampled blood. After red blood cell lysis, leukocytes were washed in 0.01 M phosphate buffered 0.85% saline (PBS) and resuspended to the original blood volume in PBS, which was then supplemented with 0.2% NaN 3 .…”

Section: Animals and Dietsmentioning

confidence: 99%

Effects of protected fish oil in the diet of periparturient dairy goats on phenotypic variation in blood and milk leukocytes

Bronzo

Puricelli

Agazzi

et al. 2010

Animal

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The goal of this study was to evaluate the effects of dietary protected fish oil (FO) on phenotypic variation in blood, milk leukocytes, and some productive and metabolic parameters in periparturient dairy goats. About 12 Alpine goats, selected from a larger group of second-parity animals, were fed from 15 days before kidding until the 15th day of lactation with the same basal diet that had been supplemented with either 47 g/head per day of FO or 47 g/head per day hydrogenated palm oil (PO). Dry matter intake, live body weight (LBW), body condition score (BCS), and productive performance were evaluated in 2 weeks after kidding. On days 15, 7, and 2 before kidding and days 2, 7, and 15 after kidding, plasma samples were collected for evaluation of alanine aminotransferase, aspartate aminotransferase, non-esterified fatty acids, glucose, beta-hydroxybutyrate, cholesterol, and urea levels. White blood cell and blood leukocyte subsets were counted in whole blood samples on the kidding day, as well as at 1, 4, and 15 days after kidding. In addition, milk somatic cell count, intramammary infection (IMI), and milk leukocyte subsets were evaluated on days 4 and 15 after kidding. No differences were observed in dry matter intake and BCS, while LBW was higher in FO-fed animals. Milk production and composition, plasma metabolites, and liver enzymes were similar in both experimental groups. Blood CD4 positive cells increased constantly ( P 5 0.05) in FO-fed group, while CD8 and CD14 cell counts significantly increased 4 days after kidding ( P , 0.01). Milk leukocyte subsets showed a significant ( P , 0.01) decrease in PO-fed group and a nonsignificant increase ( P 5 0.34) in FO-fed group, despite the presence of coagulase negative staphylococci IMI. The results of the productive performance evaluation agreed with those of many other studies, which did not find any significant differences between dairy goats fed diets enriched with FO or PO supplements. The administration of FO to dairy goats in transition appeared to affect the variation in blood leukocytes with a constant increase in CD4-and CD8-positive cells in comparison with a PO fat-supplemented diet.

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“…Although tolerance develops to the hypothermic, antinociceptive, locomotor, and immune functions of cannabinoids (Bass and Martin 2000;Massi et al 1998;Pertwee et al 1993;Welch 1997), there are some effects of THC to which tolerance does not appear to develop. For example, Nava et al (2001) reported that there was no tolerance to the behavioral effects of THC in a workingmemory test in rats (T-maze performance) or to its effects in reducing extracellular levels of hyppocampal acetylcholine.…”

Section: Cannabinoid Self-administrationmentioning

confidence: 99%

Cannabinoids: reward, dependence, and underlying neurochemical mechanisms?a review of recent preclinical data

2003

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Recent demonstrations that strong and persistent intravenous self-administration behavior can be obtained in squirrel monkeys using a range of THC doses that are in agreement with the total intake and the single doses of THC normally self-administered by humans smoking marijuana cigarettes provides a reliable and direct tool for assessing the reinforcing effects of THC that are central to its abuse liability. In addition, recent demonstrations of persistent intravenous self-administration of synthetic cannabinoid CB1 receptor agonists by rats and mice and the development of genetically modified mice lacking specific cannabinoid receptors provide convenient rodent models for exploring underlying neurochemical mechanisms. Repeated demonstrations in rats that THC and synthetic CB1 agonists can induce conditioned place preferences or aversions, depending on details of dose and spacing, can reduce the threshold for intracranial self-stimulation behavior under certain conditions, and can serve as effective discriminative stimuli for operant behavior provide less direct, but more rapidly established, measures for investigating the rewarding effects of cannabinoids. Finally, there have been numerous recent reports of major functional interactions between endogenous cannabinoid, opioid, and dopaminergic neurotransmitter systems in areas such as analgesia, physical dependence and tolerance development, and drug reinforcement or reward. This provides an opportunity to search for drugs with the beneficial therapeutic effects of currently available cannabinoids or opioids but without undesirable adverse effects such as abuse liability.

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Immune function alterations in mice tolerant to Δ9-tetrahydrocannabinol: functional and biochemical parameters

Cited by 40 publications

References 26 publications

Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages

Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages

Effects of protected fish oil in the diet of periparturient dairy goats on phenotypic variation in blood and milk leukocytes

Cannabinoids: reward, dependence, and underlying neurochemical mechanisms?a review of recent preclinical data

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