For statistical comparisons, viral loads were log10-transformed and samples below the limit of quantification were assigned the midpoint value between zero and the lower limit (25 copies)

For statistical comparisons, viral loads were log10-transformed and samples below the limit of quantification were assigned the midpoint value between zero and the lower limit (25 copies). == Lymphocyte quantification and assessment == Complete and differential blood counts were performed at the Tulane National Primate Research Center (TNPRC) using a Siemens Advia 120 Hematology System for total leukocyte counts and WrightGiemsa staining of blood smears for leukocyte differentials. contrast to our results in male animals, chronic 9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ratio, were not altered by 9-THC compared to control females; however, females that received chronic 9-THC did not gain as much weight as control animals. In addition, 9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+and CD8+T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic 9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic 9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of 9-THC and other cannabinoids around the HIV disease course and their implications for computer virus transmission. == Introduction == Substance abuse is usually prevalentin persons living with HIV/AIDS (PLWHA), with approximately 80% reporting use of an illicit drug during their lifetime.1Up to 40% of PLWHA report recent use of cannabis, more commonly known as marijuana. 26Marijuana contains numerous chemical compounds known generically as cannabinoids, including cannabidiol, cannabinol, and the major psychoactive constituent delta-9-tetrahydrocannabinol (9-THC). Among the therapeutic benefits attributed to cannabinoids are the antiemetic and hyperphagic effects for wasting syndrome in cancer and AIDS patients, pressure-lowering effects in the eye for treatment of glaucoma, and antispasmodic effects for multiple sclerosis.79Dronabinol (Marinol, AbbVie Inc., North Chicago, IL), an oral formulation of 9-THC, is also approved by the Food and Drug Administration for the management of HIV-associated anorexia. 912 Cannabinoids exert their actions largely through two cannabinoid receptors, CB1 and CB2, which are expressed in the central nervous system and in peripheral tissues.1315CB1 receptors mediate the psychotropic effects of cannabinoids, while CB2 receptors have been shown to produce immunomodulatory effects.16,17CB2 receptors are expressed on both innate and adaptive immune cells in which the level of expression is dependent upon a cell’s activation state.18,19In vitroandin vivostudies have shown that cannabinoids exert diverse immunomodulatory effects, including reducing cellular proliferation, shifting the Th1/Th2 balance, altering immune cell function, and affecting cytokine production.17,19,20Animal studies have also Cefdinir shown that immunomodulation by cannabinoids can decrease resistance to bacterial, parasitic, Cefdinir and viral infections.2125The immunosuppressive effects of 9-THC alter hostpathogen interactions and thereby impact disease pathogenesis.26,27Thus, the potential interaction of cannabinoids with HIV disease progression has been the focus of scientific attention.9 Limited clinical investigations have evaluated the impact of cannabinoids on HIV disease progression. For example, an early study noted that marijuana use was associated with progression of HIV-seropositive subjects to end-stage AIDS.28In contrast, Abramset al. evaluated the effects of both smoked and oral 9-THC on HIV contamination in a randomized, placebo-controlled study and found that short-term (21 days) administration had no harmful effects on plasma viral levels or CD4+T lymphocyte counts.29These data were also consistent with our previous studies utilizing a well-established nonhuman primate model, which examined the Mouse monoclonal to PRMT6 effects of chronic cannabinoid use on HIV disease progression. Chronic daily administration of 9-THC (0.32 mg/kg twice Cefdinir a day) to simian immunodeficiency computer virus (SIV)-infected male rhesus macaques provided protection from early mortality, along with attenuated plasma viral levels and retention of body mass.30More specifically, reduced viral loads were seen in tissue from the brain, spleen, and lymph nodes of THC/SIV+animals relative to controls, and this was associated with decreased expression of tissue proinflammatory cytokines and decreased intestinal cell death.15,31,32Together, these findings demonstrated that 9-THC could attenuate SIV disease progression in male rhesus macaques. A similar investigation had not yet been conducted to determine if chronic 9-THC would produce the same effects in Cefdinir SIV-infected female rhesus macaques. Cannabinoids have clearly been shown to exert sex-dependent biological and behavioral effects. In humans, marijuana abuse is usually more prevalent in males than females, which suggests potential differences in both the reinforcing and subjective effects of 9-THC.3335In animals, both behavioral and pharmacodynamic data support a direct interaction with gonadal hormones.36For example, Danielet al. used a within-subject design to show that estradiol administration attenuated the disruptive effects of 9-THC in ovariectomized (OVX) female rats responding in a complex learning task.37These data are also supported by pharmacodynamic data indicating that ovarian hormones can either inhibit or antagonize cannabinoid signaling in areas of the brain important for cognitive functioning, such as the hippocampus and striatum.38Moreover, estrogens appear to produce the attenuation of cannabinoid signaling in multiple.