EXPOSURE OF ADOLESCENT MICE TO Δ9-TETRAHYDROCANNABINOL SHAPES IMMUNE RESPONSE IN ADULTHOOD
Tesi di Dottorato
Data di Pubblicazione:
2014
Citazione:
EXPOSURE OF ADOLESCENT MICE TO Δ9-TETRAHYDROCANNABINOL SHAPES IMMUNE RESPONSE IN ADULTHOOD / S. Moretti ; tutor: P. Sacerdote ; direttore della Scuola: A. Panerai. DIPARTIMENTO DI SCIENZE FARMACOLOGICHE E BIOMOLECOLARI, 2014 Jan 16. 26. ciclo, Anno Accademico 2013. [10.13130/moretti-sarah_phd2014-01-16].
Abstract:
Marijuana, also called Cannabis, is the illicit drug most frequently used by human adolescents;this is facilitated by the fact that users generally perceive these drugs as relatively harmless.
Recent data estimate that cannabis use starts in the period from 12 to 18 years of age, though
even earlier use (9–10 years) is now anecdotally reported. Among the many consequences
related to the cannabis use, it is increasingly emerging as the Δ9-THC, as well as endogenous cannabinoids, are able to affect certain functions of the immune system.
In fact, studies conducted in experimental animals indicate that cannabis impairs the immune
response by altering the homeostasis of the immune system.
The adolescence is a particularly vulnerable period of individual life, both for physical and psychological maturity; also the immune system during this development period might be
particularly vulnerable to the effects induced by this drug. However, there aren't currently available studies to investigate whether the cannabis intake during adolescence period can have
a negative impact on some immune functions such as the individual's response to infection,
allergic and autoimmune pathologies, both during the period of drug intake and in adulthood, thus long time from the last direct cannabis exposure.
The purpose of this study was to investigate whether the use of cannabis during adolescence may induce immediate and delayed effects on the immune system that may then persist in adulthood.
As immune parameters we considered both innate and acquired immunity, measuring T-cells and macrophage cytokines production.
We used Balb C/J male mice, 33 post natal days (PND) as model of adolescence age and 80PND as model of adult age. Δ9-THC was administerd with increasing subcutaneous (s.c.) doses,
starting from 5 mg/kg and gradually reaching 15mg/kg in 10 days.
Control animals were treated with the vehicle for the same duration of time.
Some groups of animals were sacrificed, for the immune evaluation, immediately at the end of the treatment, while other groups of mice were housed until 90 PND before the immune evaluation.
We recently added a fourth study group consisting of adult animals treated with the drug, for 10days, and housed for 47 days, up to 137 PND, when the evaluation of immune parameters were performed. The data regarding this last study group are not completed, due to the long times
required for the implementation of the experimental protocol and refer only to the innate and acquired immunity.
In order to study acquired immunity, young and adult mice were immunized with KLH protein to induce an antigen-specific reaction and Th1/Th2 balance was assessed by measuring the production of IFN-γ, IL-4 and IL-10 by splenic lymphocytes.
In order to assess macrophage function we used peritoneal macrophages stimulated in vitro
with LPS endotoxin; IL-1β and TNF-α were assessed as pro-inflammatory cytokines, while IL-10 was evaluated as anti-inflammatory cytokine.
The cytokine production was measured by specific ELISA and Real-Time PCR.
At the end of Δ9-THC treatment in both young and adult mice, after immunization, a significant
reduction in the production of IFN-γ was observed, while the Th2 cytokines IL-4 and IL-10 were significantly increased.
When we measured immune response of adult mice treated with the drug in adolescence, we observed that the production of IFN-γ was still lower and that, in contrast to what observed
immediately at the end of treatment, also the Th2 cytokine levels were decreased compared with vehicle mice.
In adult animals, assessed 47 days after the end of treatment, there were no significant differences between Δ9-THC or vehicle groups.
We also evaluated the ability of the animals to develop an
Tipologia IRIS:
Tesi di dottorato
Keywords:
adolescent ; cytokines ; Δ9-Tetrahydrocannabinol ; immune responses ; liquid chromatography-mass spectrometry ; marijuana
Elenco autori:
S. Moretti
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