Chronic Δ⁹-Tetrahydrocannabinol Administration Reduces IgE⁺B Cells but Unlikely Enhances Pathogenic SIV_mac251 Infection in Male Rhesus Macaques of Chinese Origin

Abstract

Delta9-tetrahydrocannabinol (Δ⁹-THC) is the major psychoactive component of the cannabis plant. Δ⁹-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 Δ⁹-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 Δ⁹-THC administration using 0.32 mg/kg or placebo (PBO), i.m., twice daily for 428 days on SIV_mac251 infected male Chinese-derived rhesus macaques. Sixteen animals were divided into four study groups: Δ⁹-THC⁺SIV⁺, Δ⁹-THC⁺SIV⁻, PBO/SIV⁺ and PBO/SIV⁻ (n = 4/group). One-month after daily Δ⁹-THC or PBO administrations, macaques in groups one and three were challenged intravenously with pathogenic SIV_mac251/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 Δ⁹-THC⁺SIV⁺ and PBO/SIV⁺ macaques. Regardless of Δ⁹-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 Δ⁹-THC treatment reduced significantly the frequency of circulating IgE⁺B cells. Only one Δ⁹-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 Δ⁹-THC administration resulted in reduction of IgE⁺B cells, yet it unlikely enhanced pathogenic SIV_mac251/CNS infection in male Rhesus macaques of Chinese origin.