RESUMEN
OBJECTIVE: This study evaluated the influence of cannabis and/or cocaine use in human immunodeficiency virus (HIV)- and cytomegalovirus (CMV)-specific T-cell responses of people with HIV (PWH). RESULTS: There was a higher percentage of IL-17-producing HIV-Gag-specific CD8+ T-cells in all drug users than that in PWH non-drug users. Stratifying the drug-user groups, increased percentages of IL-17-producing HIV-Gag-specific CD4+ and CD8+ T-cells were found in PWH cannabis plus cocaine users compared to PWH non-drug users. In response to CMV, there were higher percentage of IL-17-producing CMV-specific CD8+ T-cell in PWH cocaine users than that in PWH non-drug users. Considering all drug users together, there was a higher percentage of SEB-stimulated IL-17-producing CD4+ T-cells than that in PWH non-drug users, whereas cannabis users had higher percentages of IL-17-producing CD4+ T-cells compared to non-drug users. METHODS: Cryopreserved peripheral blood mononuclear cells from 37 PWH undergoing antiretroviral therapy (ART) using cannabis (10), cocaine (7), or cannabis plus cocaine (10) and non-drug users (10) were stimulated with HIV-1 Gag or CMV-pp65 peptide pools, or staphylococcal enterotoxin B (SEB) and evaluated for IFN-γ- and/or IL-17A-producing CD4+ and CD8+ T-cells using flow cytometry. CONCLUSIONS: Cannabis plus cocaine use increased HIV-specific IL-17 producing T-cells and cocaine use increased IL-17 CMV-specific CD8+ T-cell responses which could favor the inflammatory conditions associated with IL-17 overproduction.
RESUMEN
OBJECTIVES: To evaluate the effects of cannabis and/or cocaine use on inflammatory, oxidative stress status and circulating monocyte subsets in HIV-infected individuals under antiretroviral therapy. DESIGN: Soluble CD14 (sCD14), intestinal fatty acid-binding protein (IFABP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and oxidative stress markers were examined. The monocyte subsets and their activation and cytokine production by peripheral blood mononuclear cells (PBMCs) of HIV-1 infected individuals upon lipopolysaccharide (LPS)-stimulation were also investigated. METHODS: sCD14, IFABP, TNF-α, IL-6, IL-8 and IL-10 levels were evaluated using ELISA, CRP by turbidimetry; lipid peroxidation (TBARS) spectrofluometrically and total thiol levels by using 5-5'-dithio-bis (2-nitrobenzoic acid) reagent. Monocyte subsets and activation were assessed by flow cytometry. RESULTS: All HIV-infected drug user groups showed higher sCD14 levels compared with HIV+ nondrug users. IFABP was increased in HIV+ drug-users in relation to healthy individuals. Cannabis use lowered the percentages of inflammatory, nonclassical, activated-classic and activated-inflammatory monocytes. Cocaine users showed increased plasmatic TNF-α and TBARS levels, decreased thiols content and lower activated-classic and inflammatory-monocyte percentages. Cannabis-plus-cocaine use increased CRP, IL-8 and IL-6/IL-10 ratio, but decreased thiol content, and inflammatory and activated-classic monocyte percentages. PBMCs of cannabis and cannabis-plus-cocaine users showed low-potential cytokine production either spontaneously or under LPS-stimulation. CONCLUSION: In HIV infection, the use of cannabis induces predominantly an anti-inflammatory profile. The use of cocaine and cannabis-plus-cocaine showed a mixed pro-inflammatory and anti-inflammatory profile, with predominance of inflammatory status. Further studies are required to better understand the action of these drugs in HIV infection.
