Interleukin-10 polymorphisms and susceptibility to ARV associated hepatotoxicity

Singh, HariOm; Samani, Dharmesh; Nain, Sumitra; Tn, Dhole

doi:10.1016/j.micpath.2019.103544

Cited by 6 publications

(6 citation statements)

References 46 publications

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“…Several inflammatory cytokines are known to modulate HIV infection/replication in vitro, with their effects being either stimulatory (TNF-α, IL-1β, IL-6, and IL-8) or inhibitory (IFN-α and IL-10). As a potent anti-inflammatory cytokine, IL-10 can counteract the adverse effects of pro-inflammatory cytokines on HIV infection and inhibit HIV replication [51]. Therefore, it is likely that imiquimod-induced IL-10 compromises the stimulatory effects of the pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) on HIV infection/replication in macrophages.…”

Section: Discussionmentioning

confidence: 99%

TLR7 Activation of Macrophages by Imiquimod Inhibits HIV Infection through Modulation of Viral Entry Cellular Factors

Meng

Liu

Wang

et al. 2021

Biology

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The Toll-like receptor (TLR) 7 is a viral sensor for detecting single-stranded ribonucleic acid (ssRNA), the activation of which can induce intracellular innate immunity against viral infections. Imiquimod, a synthetic ligand for TLR7, has been successfully used for the topical treatment of genital/perianal warts in immunocompetent individuals. We studied the effect of imiquimod on the human immunodeficiency virus (HIV) infection of primary human macrophages and demonstrated that the treatment of cells with imiquimod effectively inhibited infection with multiple strains (Bal, YU2, and Jago) of HIV. This anti-HIV activity of imiquimod was the most potent when macrophages were treated prior to infection. Infection of macrophages with pseudotyped HIV NL4-3-ΔEnv-eGFP-Bal showed that imiquimod could block the viral entry. Further mechanistic studies revealed that while imiquimod had little effect on the interferons (IFNs) expression, its treatment of macrophages resulted in the increased production of the CC chemokines (human macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, and upon activation regulated normal T cells expressed and secreted (RANTES)), the natural ligands of HIV entry co-receptor CCR5, and decreased the expression of CD4 and CCR5. The addition of the antibodies against the CC chemokines to macrophage cultures could block imiquimod-mediated HIV inhibition. These findings provide experimental evidence to support the notion that TLR7 participates in the intracellular immunity against HIV in macrophages, suggesting the further clinical evaluation of imiquimod for its additional benefit of treating genital/perianal warts in people infected with HIV.

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Section: Discussionmentioning

confidence: 99%

TLR7 Activation of Macrophages by Imiquimod Inhibits HIV Infection through Modulation of Viral Entry Cellular Factors

Meng

Liu

Wang

et al. 2021

Biology

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“…Outro estudo demonstrou que pacientes em uso de efavirenz com polimorfismos no gene da interleucina 10 (citocina que impede a replicação do vírus HIV na fase inicial da doença) apresentam maior predisposição à hepatotoxicidade associada aos antirretrovirais, sobretudo nos pacientes que adicionalmente fazem o uso de tabaco. No mesmo estudo, pacientes com o genótipo-819TT que já possuíam hepatotoxicidade exibiram maior risco de severidade da doença (Singh, Samani, Nain, & Dhole, 2019). Neste aspecto, a farmacogenética ainda consiste em um campo de pesquisa incipiente, sendo necessária a realização de mais estudos visando preencher as lacunas existentes (Metzger, Souza-Costa, & Tanus-Santos, 2006).…”

Section: Polimorfismo Genéticounclassified

Alterações farmacocinéticas de antirretrovirais em situações especiais: uma revisão narrativa

Bernardes

Sales

Santos

et al. 2021

RSD

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O número de novos casos de infecção pelo HIV tem aumentado continuamente. No cenário mundial, nota-se a ampliação do acesso à terapia antirretroviral e, atualmente, 26 milhões de pessoas fazem uso de antirretrovirais. No Brasil, país que fornece acesso integral e gratuito aos antirretrovirais, cerca de 630 mil pessoas encontram-se em tratamento. O presente estudo tem o objetivo de descrever as alterações farmacocinéticas dos antirretrovirais em pacientes com condições fisiológicas distintas. Realizou-se um levantamento bibliográfico com estudos relativos ao uso de antirretrovirais em grupos específicos: extremos de idade (recém-nascidos e idosos), gravidez, doença hepática, doença renal crônica, doença cardiovascular, obesidade, alterações metabólicas, interações alimentares, uso e abuso de drogas lícitas e ilícitas e polimorfismo genético. Em determinadas situações, verificou-se alterações em parâmetros farmacocinéticos como absorção, distribuição, metabolismo e excreção, assim como, variações dos níveis plasmáticos dos antirretrovirais. Destaca-se nos grupos investigados, a importância do ajuste de dose para aumentar a efetividade dos antirretrovirais e proporcionar um tratamento mais adequado às pessoas vivendo com HIV.

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“…SNPs in IL-10 and HIV-1 susceptibility were included (10 articles for rs1800896, 11 for rs1800872 and 3 for rs1800871 SNP) ( Table 1). Overall, 24 case-control studies with 3957 cases of HIV-1 as well as 4845 controls were included [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. The controls were mainly healthy individuals.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Many published studies have suggested relationships between IL-10 gene variations and HIV-1 risk [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], including previous two meta-analysis [34,35]. However, ambiguous conclusions have been reported, it is necessary to do an undated meta-analysis including all the currently studies to reanalyze in time.…”

Section: Introductionmentioning

confidence: 99%

Association between polymorphisms (rs1800896, rs1800872, rs1800871) in IL-10 gene with human immunodeficiency virus 1-infected patients’ susceptibility

Tai¹,

Li²,

Zhou³

et al. 2020

Preprint

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Background Interleukin-10 (IL-10) is considered to play a role in the human immunodeficiency virus-1 (HIV-1) infections, and 3 common single nucleotide polymorphisms (SNPs), perhaps have an association with HIV-1 risk. Methods To find out the above doubt, we performed a comprehensive analysis to assess the relationship between IL-10 polymorphisms and HIV-1. The PubMed database were chosen to identify potential articles through Feb 21, 2020. The odds ratio with 95% confidence interval (OR with 95%CI) was calculated to evaluate the strength of the relationships. Results There have 15 different articles including 24 case-control studies including those on three different SNPs in IL-10 for HIV-1 were found. Positive increased or damaged associations were detected for rs1800872C/A with HIV-1 risk in total (such as: OR with 95%CI = 1.22 with 1.02–1.41 for A-allele vs. C-allele model), and Asians (such as: OR with 95%CI = 1.51 with 1.07–1.88 for AA vs. CC model), population-based, PCR-RFLP, sequence subgroups. Moreover, increased associations were also detected between rs1800871C/T SNP (OR with 95%CI = 1.47 with 1.08-2.00 for CC vs. CT + TT model). No association was found for rs1800896. Conclusion Our current study indicated that two SNPs (rs1800872C/A and rs1800871C/T) in IL-10 perhaps be potentially associated with the susceptibility for developing HIV-1 infection.

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Interleukin-10 polymorphisms and susceptibility to ARV associated hepatotoxicity

Cited by 6 publications

References 46 publications

TLR7 Activation of Macrophages by Imiquimod Inhibits HIV Infection through Modulation of Viral Entry Cellular Factors

TLR7 Activation of Macrophages by Imiquimod Inhibits HIV Infection through Modulation of Viral Entry Cellular Factors

Alterações farmacocinéticas de antirretrovirais em situações especiais: uma revisão narrativa

Association between polymorphisms (rs1800896, rs1800872, rs1800871) in IL-10 gene with human immunodeficiency virus 1-infected patients’ susceptibility

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