Avaliação, in vitro, da influência dos antiretrovirais zidovudina, lamivudina, efavirenz e lopinavir/ritonavir isolados ou associados sobre a função fagocitária e produção de radicais de oxigênio por neutrófilos e monócitos de indivíduos normais

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

The introduction of highly active antiretroviral therapy (HAART) in 1996 has decreased the morbidity and the mortality rates associated with the HIV infection. Though the infection can be controlled by antiretrovirals, these medicines may cause undesirable side effects due to their capacity to interact with cells of patients. It has been reported that these drugs may modulate the innate and adaptative immnune system. However, few is known about the influences on immune functions by protocols routinely used in the treatment of HIV infected patients, constituted by reverse transcriptase and protease inhibitors, because most of researches have just investigated the influence restricted to isolated drugs. So, this work aimed to evaluate the influence of the isolate treatment with zidovudine (AZT), lamivudine (3TC), efavirenz (EFV), lopinavir/ritonavir (LPV/RTV) and of the associations AZT/3TC/EFV or AZT/3TC/LPV/RTV on phagocytic capacity and superoxide production by neutrophils and monocytes of healthy individuals, in vitro. It was collected 20 ml of peripheral blood from 20 healthy volunteers and the phagocytic capacity was assessed through pathogen-associated molecular patterns receptors (PAMPr) and through opsonin receptors. The drugs were used on maximum plasma levels considering pharmacokinetic studies after ingestion and the concentration applied for each one was 1,64 μg/ml for AZT, 1,5μg/ml for 3TC, 3,7 μg/ml for EFV and 11,45 μg/ml and 2,86 μg/ml for LPV and RTV, respectively. The phagocytic index was calculated as the average number of ingested Saccharomyces cerevisiae per phagocyte multiplied by the percentage of these cells engaged in phagocytosis. The oxidative capacity was assessed by the nitroblue tetrazolium (NBT) test. The isolated treatment with EFV increased the percentual of neutrophils engaged in phagocytosis through PAMPr (p=0,004) and through opsonin receptors (p=0,020), while the preincubation with LPV/RTV (p=0,024) and AZT/3TC/LPV/RTV (p=0,008) for 60 minutes decreased neutrophil phagocytic index when phagocytosis through PAMPr was investigated. The pretreatment of phagocytes for 30 minutes with LPV/RTV increased the monocyte phagocytic capacity through PAMPr (p=0,003) due to both the increase of the ingested yeasts average and the percentual of monocytes involved in phagocytosis, similar to the result observed to the pretreatment of these cells with AZT/3TC/LPV/RTV for 30 minutes and tended to increase (p=0,077) the percentual of neutrophils engaged in phagocytosis through opsonin receptors. However, when LPV/RTV was incubated with monocytes for 60 minutes, the monocyte phagocytic index through PAMPr decreased (p=0,013) due to the diminished percentual of monocytes engaged in phagocytosis. The LPV/RTV isolately decreased the monocyte phagocytic capacity (p=0,020) due to the reduction of the number of ingested yeasts by these cells. The AZT tended to increase the monocyte phagocytic capacity when phagocytosis through PAMPr was analyzed (p=0,097), because it tended to increase the percentual of monocytes engaged in phagocytosis. The production of reactive oxygen species (ROS) were more intensely influenced by the studied antiretrovirals. The AZT (p=0,027) and the 3TC (p=0,004) isolately and the associations LPV/RTV (p=0,0001) and AZT/3TC/LPV/RTV (p=0,0001) decreased the stimulated production of ROS by phagocytes. The percentual of baseline NBT reduction was also depressed by the associations LPV/RTV (p=0,0007) e AZT/3TC/LPV/RTV (p<0,0001) and tended to be reduced by the treatment with 3TC alone (p=0,071). These results suggest that the protocol AZT/3TC/EFV can be more adequate to the initial treatment of those individuals infected by HIV because it has not changed the phagocytic capacity or ROS production by neutrophils and monocytes, while the association AZT/3TC/LPV/RTV could be more interesting to patients with intolerance or viral resistance to EFV. It is also possible that patients with multiple resistances to antiretrovirals can be benefited by protocols containing LPV/RTV, because the reduction of ROS determined by these drugs, as demonstrated in this research, can contribute for the lowest rates of viral replication, lymphocyte apoptosis and HIV-related neurodegeneration.

ASSUNTO(S)

neutrófilos monócitos zidovudina ânion superóxido antiretrovirais fagócitos lopinavir efavirenz ciencias da saude radicais de oxigênio lamivudina ritonavir

ACESSO AO ARTIGO

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