Marijuana abuse is prominent among adolescents. Although Δ9-THC, one of its main components, has been demonstrated to modulate immunity in adults, little is known about its impact during adolescence on the immune system and the long-lasting effects in adulthood. We demonstrate that 10 days of Δ9-THC treatment induced a similar alteration of macrophage and splenocyte cytokines in adolescent and adult mice. Immediately at the end of chronic Δ9-THC, a decrease of proinflammatory cytokines IL- 1β and TNF-α and an increase of anti-inflammatory cytokine IL-10 production by macrophages were present as protein and mRNA in adolescent and adult mice. In splenocytes, Δ9-THC modulated Th1/Th2 cytokines skewing toward Th2: IFN-γ was reduced, and IL-4 and IL-10 increased. These effects were lost in adult animals, 47 days after the last administration. In contrast, in adult animals treated as adolescents, a perturbation of immune responses, although in an opposite direction, was present. In adults treated as adolescents, a proinflammatory macrophage phenotype was observed (IL-1β and TNF-α were elevated; IL-10 decreased), and the production of Th cytokines was blunted. IgM titers were also reduced. Corticosterone concentrations indicate a long-lasting dysregulation of HPA in adolescent mice. We measured blood concentrations of Δ9-THC and its metabolites, showing that Δ9-THC plasma levels in our mice are in the order of those achieved in human heavy smokers. Our data demonstrate that Δ9-THC in adolescent mice triggers immune dysfunctions that last long after the end of abuse, switching the murine immune system to proinflammatory status in adulthood.
Delta(9)-Tetrahydrocannabinol-induced anti-inflammatory responses in adolescent mice switch to proinflammatory in adulthood / S. Moretti, M. Castelli, S. Franchi, M.A. Raggi, L. Mercolini, M. Protti, L. Somaini, A.E. Panerai, P. Sacerdote. - In: JOURNAL OF LEUKOCYTE BIOLOGY. - ISSN 0741-5400. - 96:4(2014 Oct), pp. 523-534.
|Titolo:||Delta(9)-Tetrahydrocannabinol-induced anti-inflammatory responses in adolescent mice switch to proinflammatory in adulthood|
MORETTI, SARAH (Primo)
SACERDOTE, PAOLA GIUSEPPINA (Corresponding)
|Parole Chiave:||Cytokines; Immune response; Liquid chromatography-mass spectrometry; Marijuana|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||ott-2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1189/jlb.3HI0713-406RR|
|Appare nelle tipologie:||01 - Articolo su periodico|