Historique
Périodique
Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway
(Le delta-9-tétrahydrocannabinol inhibe l'immunité antitumorale en augmentant la production de cytokines immunodépressives via le récepteur CB2.)
Auteur(s) :
ZHU L. X. ;
SHARMA, S. ;
STOLINA M. ;
GARDNER B. ;
ROTH, M. D. ;
TASHKIN D. P. ;
DUBINETT S. M.
Année
2000
Page(s) :
373-380
Langue(s) :
Anglais
Refs biblio. :
91
Domaine :
Drogues illicites / Illicit drugs
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Thésaurus mots-clés
CANNABINOIDES
;
SYSTEME IMMUNITAIRE
;
CANCER
;
DEFICIT IMMUNITAIRE
;
EFFET SECONDAIRE
;
MODELE ANIMAL
Note générale :
Journal of Immunology (the), 2000, (165), 373-380
Note de contenu :
graph. ; tabl.
Résumé :
ENGLISH :
In this study, we show that delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, suppresses host immune reactivity against lung cancer. In two different weakly immunogenic murine lung cancer models, intermittent administration of THC (5 mg/kg, four times/wk i.p. for 4 wk) led to accelerated growth of tumor implants compared with treatment with diluent alone. In contrast to our findings in immunocompetent mice, THC did not affect tumor growth in tumor-bearing SCID mice. The immune inhibitory cytokines, IL-10 and TGF-b, were augmented, while IFN-y was down-regulated at both the tumor site and in the spleens of THC-treated mice. Administration of either anti-IL-10- or anti-TGF-b-neutralizing Abs prevented the THC-induced enhancement in tumor growth. Both APC and T cells from THC-treated mice showed limited capacities to generate alloreactivity. Furthermore, lymphocytes from THC-treated mice transferred the effect to normal mice, resulting in accelerated tumor growth similar to that seen in the THC-treated mice. THC decreased tumor immunogenicity, as indicated by the limited capacity for tumor-immunized, THC-treated mice to withstand tumor rechallenge. In vivo administration of a specific antagonist of the CB2 cannabinoid receptor also blocked the effects of THC. Our findings suggest the THC promotes tumor growth by inhibiting antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. (Author' s abstract)
Affiliation :
Pulmonary Immunology Laboratory and Division of Pulmonary and Critical Care Medicine, Univ. of California, Los Angeles, School of Medicine, Los Angeles, CA 90095
Etats-Unis. United States.
Etats-Unis. United States.