Avaliação de parâmetros imunológicos, inflamatórios e bioquímicos em pacientes HIV-positivos sob uso da terapia antirretroviral em associação com a própolis
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Data
2021-04-07
Autores
Conte, Fernanda Lopes [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A infecção pelo HIV representa um grave problema de saúde pública no mundo, contando com milhões de pessoas infectadas e novos casos registrados anualmente. A terapia antirretroviral (TARV) mudou completamente o cenário da infecção, propiciando marcante redução da mortalidade das pessoas que vivem com HIV/aids (PVHA). Apesar dos benefícios da TARV, seu uso crônico pode resultar em efeitos adversos, como citotoxicidade e distúrbios metabólicos, processos que contribuem com a persistente ativação imune e estado inflamatório intenso que as PVHA apresentam. Assim, objetivamos investigar se a própolis, produto apícola que possui inúmeras propriedades terapêuticas, seria capaz de promover benefícios à saúde de PVHA assintomáticas em uso de TARV. Para isso, após randomização de 40 pacientes em caráter duplo-cego, os dois grupos (500 mg/dia própolis versus placebo) foram analisados em dois momentos: antes (M0) e 3 meses após (M1) a intervenção. Resultados da carga viral plasmática do HIV, contagem de células T CD4+/CD8+, hemograma e o perfil bioquímico/metabólico foram obtidos via prontuário eletrônico. A concentração de citocinas plasmáticas (TNF-α, IL-6, IL-10, IL-17, IL-2 e IL-4) e a proliferação de linfócitos foram determinadas por citometria de fluxo. A produção de citocinas (IFN-γ, IL-5, IL-17, IL-10, IL-18, IL-1β e IL-33) por células mononucleares do sangue periférico (PBMC) foi determinada por método imunoenzimático (ELISA). A expressão dos genes T-bet, GATA-3, RORγt e Foxp3 foi avaliada pela reação em cadeia da polimerase quantitativa em tempo real (RT-qPCR). Houve aumento na atividade de creatinofosfoquinase no grupo tratado com própolis, embora sem significância clínica. Observou-se, no mesmo grupo, aumento na concentração de magnésio, correlação positiva entre IL-10 (citocina anti-inflamatória) e contagem de células T CD4+, correlação negativa entre IL-10 e IFN-γ (citocina pró-inflamatória), além do aumento da expressão de Foxp3 e da proliferação de linfócitos T CD4+. Assim, os resultados indicam que o uso da própolis é seguro e pode ser uma alternativa para melhora da resposta imune e redução da inflamação nos pacientes assintomáticos, através da indução de células T reguladoras. Resultados adicionais obtidos com linhagem celular de monócitos humanos, em projeto paralelo, indicaram que a própolis exerce atividade antioxidante, potencialmente envolvida em sua ação anti-inflamatória e antialérgica, o que também pode ser uma contribuição para as PVHA. No entanto, mais estudos são necessários para confirmar esses achados e poder considerar a própolis uma intervenção efetiva para as PVHA, em especial àquelas com comorbidades ou falha terapêutica, não contempladas neste estudo.
HIV infection represents a serious public health problem in the world, with millions of people infected and new cases registered annually. Antiretroviral therapy (ART) has completely changed the infection scenario, providing a marked reduction in the mortality of people living with HIV/AIDS (PLWHA). Despite the benefits of the ART, its chronic use can lead to side effects such as cytotoxicity and metabolic disorders, what contributes to persistent immune activation and inflammatory status in PLWHA. Thus, we aimed to investigate whether propolis, a bee product presenting several therapeutic properties, could be able to improve the health of asymptomatic PLWHA under ART. After a double-blind randomization of 40 patients, two groups (500 mg/day propolis versus placebo) were analyzed in two moments: before (M0) and 3 months after (M1) the intervention. Plasma HIV viral load, CD4+ /CD8+ T cell count, complete blood count and biochemical/metabolic profile were obtained via electronic medical record. The concentration of plasma cytokines (TNF-α, IL-6, IL-10, IL-17, IL2 and IL-4) and lymphocyte proliferation were determined by flow cytometry. The production of cytokines (IFN-γ, IL-5, IL-17, IL-10, IL-18, IL-1β and IL-33) by peripheral blood mononuclear cells (PBMC) was determined by Enzyme-Linked Immunosorbent Assay (ELISA). The expression of the T-bet, GATA-3, RORγt and Foxp3 genes was evaluated by real time reverse transcription polymerase chain reaction (RT-qPCR). There was an increase in creatinophosphokinase activity after propolis intake, although without clinical significance. The same group also showed increased magnesium levels, a positive correlation between IL-10 (anti-inflammatory cytokine) and CD4+ T cell count, a negative correlation between IL-10 and IFN-γ (proinflammatory cytokine), an increased Foxp3 expression and CD4+ T lymphocytes proliferation. Our findings indicate that the use of propolis is safe and may be an alternative for improving the immune response and reducing inflammation in asymptomatic patients, inducing regulatory T cells. Additional findings were obtained using a human monocytic cell line in a parallel project, indicating that propolis exerted an antioxidant activity, potentially involved in its anti-inflammatory and antiallergic action, what can also be a contribution to PLWHA. However, more studies are needed to confirm these findings and consider propolis an effective intervention for PLWHA, especially those with comorbidities or therapeutic failures, who was not included in this study.
HIV infection represents a serious public health problem in the world, with millions of people infected and new cases registered annually. Antiretroviral therapy (ART) has completely changed the infection scenario, providing a marked reduction in the mortality of people living with HIV/AIDS (PLWHA). Despite the benefits of the ART, its chronic use can lead to side effects such as cytotoxicity and metabolic disorders, what contributes to persistent immune activation and inflammatory status in PLWHA. Thus, we aimed to investigate whether propolis, a bee product presenting several therapeutic properties, could be able to improve the health of asymptomatic PLWHA under ART. After a double-blind randomization of 40 patients, two groups (500 mg/day propolis versus placebo) were analyzed in two moments: before (M0) and 3 months after (M1) the intervention. Plasma HIV viral load, CD4+ /CD8+ T cell count, complete blood count and biochemical/metabolic profile were obtained via electronic medical record. The concentration of plasma cytokines (TNF-α, IL-6, IL-10, IL-17, IL2 and IL-4) and lymphocyte proliferation were determined by flow cytometry. The production of cytokines (IFN-γ, IL-5, IL-17, IL-10, IL-18, IL-1β and IL-33) by peripheral blood mononuclear cells (PBMC) was determined by Enzyme-Linked Immunosorbent Assay (ELISA). The expression of the T-bet, GATA-3, RORγt and Foxp3 genes was evaluated by real time reverse transcription polymerase chain reaction (RT-qPCR). There was an increase in creatinophosphokinase activity after propolis intake, although without clinical significance. The same group also showed increased magnesium levels, a positive correlation between IL-10 (anti-inflammatory cytokine) and CD4+ T cell count, a negative correlation between IL-10 and IFN-γ (proinflammatory cytokine), an increased Foxp3 expression and CD4+ T lymphocytes proliferation. Our findings indicate that the use of propolis is safe and may be an alternative for improving the immune response and reducing inflammation in asymptomatic patients, inducing regulatory T cells. Additional findings were obtained using a human monocytic cell line in a parallel project, indicating that propolis exerted an antioxidant activity, potentially involved in its anti-inflammatory and antiallergic action, what can also be a contribution to PLWHA. However, more studies are needed to confirm these findings and consider propolis an effective intervention for PLWHA, especially those with comorbidities or therapeutic failures, who was not included in this study.
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Palavras-chave
HIV/aids, Imunomodulação, Inflamação, Própolis, Terapia antirretroviral