La sucralosa promueve la polarización a macrófagos proinflamatorios M1

RESUMEN La sucralosa es un edulcorante no calórico de amplio consumo a nivel mundial, es considerado como un aditivo seguro, debido a que es eliminado en periodos cortos de tiempo. Recientemente se evidenció su bioacumulación en tejido adiposo, donde se encuentran inmersos macrófagos, células del sistema inmune involucradas en el desarrollo de la inflamación sistémica de bajo grado. A la fecha, no se cuenta con suficiente información para demostrar si los edulcorantes potencian los procesos inflamatorios alterando la función de células presentes en tejido y/o contribuyen en el desarrollo de patologías metabólicas. Por lo anterior, en nuestro trabajo se evaluó el efecto de la sucralosa en la viabilidad de los macrófagos diferenciados de la línea celular monocítica THP-1, por azul de tripán y ensayos de MTT, así como su efecto en la polarización M1/M2 por PCR según la expresión de IRF4, IRF5, STAT1, STAT6, perfil de expresión de IL-6, IL-12, TNF-α, TGF-β, IL-10 y SOCS3 por qPCR, y la cuantificación de la quimiocina IP-10 por ELISA. Los resultados indicaron que la sucralosa no tiene efectos citotóxicos, pero disminuye el número de células viables metabólicamente activas determinadas por MTT de manera dependiente de la concentración. La sucralosa incrementa la concentración de la quimiocina IP-10 y la expresión génica del factor de transcripción IRF5 y disminuye la expresión de IRF4 y STAT6, favoreciendo la polarización hacia poblaciones M1. La bioacumulación de sucralosa en tejido adiposo, y su interacción con macrófagos, podría inducir su polarización a M1.

ABSTRACT Sucralose is a non-nutritive sweetener widely consumed worldwide; it is considered a safe additive because it is eliminated quickly. Recently its bioaccumulation in adipose tissue was evidenced, where macrophages, cells of the immune system involved in developing low-grade systemic inflammation, are found. To date, there is a paucity of information regarding whether sweeteners potentiate inflammatory processes by altering the function of cells present in tissue and/or contribute to the development of metabolic pathologies. We evaluate the effect of sucralose on the viability of differentiated macrophages of the monocytic cell line THP-1, by trypan blue and MTT assays, respectively, as well as its effect on M1/ M2 by PCR according to the expression of IRF4, IRF5, STAT1, STAT6, expression profile of IL6, IL-12, TNF-α, TGF-β, IL-10 and SOCS3 by qPCR, and the quantification of the chemokine IP-10 by ELISE. The results indicated that sucralose has no cytotoxic effects but decreases the number of metabolically active viable cells determined by MTT of macrophages in a concentration-dependent manner. Sucralose increased the concentration of the chemokine IP-10 and the gene expression of the transcription factors IRF5 and decreased the expression of IRF4 and STAT 6 gene expression, favoring polarization towards M1 populations. The bioaccumulation of sucralose in adipose tissue, and its interaction with macrophages, could induce its polarization to M1.

Th17 Lymphocytes in Children with Asthma: Do They Influence Control?

Background: Allergic asthma was considered as an inflammation mediated by specific CD4+ helper lymphocytes (Th2); however, this paradigm changed in 2005, when a third group of helper cells called Th17 cells were identified. Th17 lymphocytes are the main source of interleukin (IL)-17A-F, IL-21, and IL-22; however, their physiological role in children is unclear. This study aimed to determine the percentage of Th17 cells and IL-17A in pediatric patients diagnosed with asthma and to associate it with disease control using a validated questionnaire. Methods: This cross-sectional, prospective, comparative study included 92 asthma-diagnosed children 4-18 years of age. The Asthma Control Test was used as an assessment measure to classify patients as controlled (n = 30), partially controlled (n = 31), and uncontrolled (n = 31). Th17 cells and IL-17A were analyzed by flow cytometry. Patients receiving inhaled steroid therapy as monotherapy or associated with a long-acting bronchodilator were included. Results: The mean percentage of Th17 cells in the participants was 4.55 ± 7.34 (Controlled), 5.50 ± 8.09 (Partially Controlled), and 6.14 ± 7.11 (Uncontrolled). There was no significant difference between the 3 groups (P = 0.71). The mean percentage of IL-17A in all the participants was 9.84 ± 9.4 (Controlled), 10.10 ± 10.5 (Partially Controlled), and 11.42 ± 8.96 (Uncontrolled); no significant difference between the 3 groups (P = 0.79) was observed. Th17 lymphocyte levels were similar among the 3 groups and the same trend was observed with IL-17A. A significant correlation between Th17 or IL-17A and the degree of asthma control (Th17, P = 0.24; IL-17A, P = 0.23) was not found. Conclusions: The percentages of both Th17 lymphocytes and IL-17A found in children with asthma were not significantly different in the 3 groups, which suggests that they do not play an important role in asthma control. Our findings may contribute to the knowledge related to non-Th2 inflammation in children. Clinical-Trials.gov ID: 2015-2102-85.

Modulation of rotavirus severe gastroenteritis by the combination of probiotics and prebiotics.

Annual mortality rates due to infectious diarrhea are about 2.2 million; children are the most vulnerable age group to severe gastroenteritis, representing group A rotaviruses as the main cause of disease. One of the main factors of rotavirus pathogenesis is the NSP4 protein, which has been characterized as a viral toxin involved in triggering several cellular responses leading to diarrhea. Furthermore, the rotavirus protein NSP1 has been associated with interferon production inhibition by inducing the degradation of interferon regulatory factors IRF3, IRF5, and IRF7. On the other hand, probiotics such as Bifidobacterium and Lactobacillus species in combination with prebiotics such as inulin, HMO, scGOS, lcFOS have been associated with improved generalized antiviral response and anti-rotavirus effect by the reduction of rotavirus infectivity and viral shedding, decreased expression of NSP4 and increased levels of specific anti-rotavirus IgAs. Moreover, these probiotics and prebiotics have been related to shorter duration and severity of rotavirus diarrhea, to the prevention of infection and reduced incidence of reinfections. In this review we will discuss in detail about the rotavirus pathogenesis and immunity, and how probiotics such as Lactobacillus and Bifidobacterium species in combination with prebiotics have been associated with the prevention or modulation of rotavirus severe gastroenteritis.