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 mgkg 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(-), PBOSIV() and PBOSIV(-) (n 4group). One-month after daily Δ(9)-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIVmac251CNS, 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 PBOSIV() macaques. Regardless of Δ(9)-THC, all infected macaques displayed significant drop of CD4CD8 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 PBOSIV() 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 SIVmac251CNS infection in male Rhesus macaques of Chinese origin.