Titre : | Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway |
Titre traduit : | (Le delta-9-tétrahydrocannabinol inhibe l'immunité antitumorale en augmentant la production de cytokines immunodépressives via le récepteur CB2.) |
Auteurs : | ZHU L. X. ; S. SHARMA ; STOLINA M. ; GARDNER B. ; M. D. ROTH ; TASHKIN D. P. ; DUBINETT S. M. |
Type de document : | Périodique |
Année de publication : | 2000 |
Format : | 373-380 / graph. ; tabl. |
Note générale : |
Journal of Immunology (the), 2000, (165), 373-380 |
Langues: | Anglais |
Discipline : | PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods) |
Mots-clés : |
Thésaurus mots-clés CANNABINOIDES ; SYSTEME IMMUNITAIRE ; CANCER ; DEFICIT IMMUNITAIRE ; EFFET SECONDAIRE ; MODELE ANIMAL |
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) |
Note de contenu : | graph. ; tabl. |
Domaine : | Drogues illicites / Illicit drugs |
Refs biblio. : | 91 |
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. |
Numéro Toxibase : | 205899 |
Centre Emetteur : | 02 Coordonnateur |
Exemplaires
Disponibilité |
---|
aucun exemplaire |
Accueil