Chronic Δ(9)-Tetrahydrocannabinol Administration Reduces IgE(+)B Cells but Unlikely Enhances Pathogenic SIVmac251 Infection in Male Rhesus Macaques of Chinese Origin.
Delta9-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive component of the cannabis plant. Δ(9)-THC has been used in the active ingredient of Marinol as an appetite stimulant for AIDS patients. Its impact on progression of HIV-1 infection, however, remains debatable. Previous studies indicated that Δ(9)-THC administration enhanced HIV-1 infection in huPBL-SCID mice but seemingly decreased early mortality in simian immunodeficiency virus (SIV) infected male Indian-derived rhesus macaques. Here, we determine the chronic effect of Δ(9)-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIVmac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ(9)-THC(+)SIV(+), Δ(9)-THC(+)SIV(-), PBO/SIV(+) and PBO/SIV(-) (n = 4/group). One-month after daily Δ(9)-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251/CNS, which was isolated from the brain of a Chinese macaque with end-staged neuroAIDS. No significant differences in peak and steady state plasma viral loads were seen between Δ(9)-THC(+)SIV(+) and PBO/SIV(+) macaques. Regardless of Δ(9)-THC, all infected macaques displayed significant drop of CD4/CD8 T cell ratio, loss of CD4(+) T cells and higher persistent levels of Ki67(+)CD8(+) T cells compared with uninfected animals. Moreover, long-term Δ(9)-THC treatment reduced significantly the frequency of circulating IgE(+)B cells. Only one Δ(9)-THC(+)SIV(+) macaque died of simian AIDS with paralyzed limbs compared with two deaths in the PBO/SIV(+) group during the study period. These findings indicate that chronic Δ(9)-THC administration resulted in reduction of IgE(+)B cells, yet it unlikely enhanced pathogenic SIVmac251/CNS infection in male Rhesus macaques of Chinese origin.
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, No.5, Panjiayuan, Nanli, Chaoyang District, Beijing, People's Republic of China.
Qiang
Q
Wei
AIDS Institute and Research Center for Infection and Immunology, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, People's Republic of China.|HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Lab of Emerging Infectious Diseases and Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, People's Republic of China.
Li
L
Liu
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, No.5, Panjiayuan, Nanli, Chaoyang District, Beijing, People's Republic of China.
Zhe
Z
Cong
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, No.5, Panjiayuan, Nanli, Chaoyang District, Beijing, People's Republic of China.
Xiaoxian
X
Wu
HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Lab of Emerging Infectious Diseases and Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, People's Republic of China.
Hui
H
Wang
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College, No.5, Panjiayuan, Nanli, Chaoyang District, Beijing, People's Republic of China.
Chuan
C
Qin
Department of Physiology, The Louisiana State University Health Sciences Center at New Orleans, 1901 Perdido Street, New Orleans, LA 70112, United States of America.
Patricia
P
Molina
AIDS Institute and Research Center for Infection and Immunology, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, People's Republic of China.|HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Guangdong Key Lab of Emerging Infectious Diseases and Shenzhen Key Lab of Infection and Immunity, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, People's Republic of China.
Zhiwei
Z
Chen
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D002681:China; D013759:Dronabinol / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D007073:Immunoglobulin E / Q000097:blood* / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood* / Q000276:immunology; D015302:Simian Immunodeficiency Virus
D007073:Immunoglobulin E; D013759:Dronabinol
AIDS; Cannabinoids; HIV-1; IgE+B cell; Rhesus macaque; SIV; THC