Obesity, inflammation and the immune system

Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.     

Eating habits and total and abdominal fat in Spanish adolescents: influence of physical activity. The AVENA study

ObjectiveTo evaluate the association between specific dietary habits and body fatness in Spanish adolescents, and to analyze the role of leisure-time physical activity (LTPA) in this association.MethodsIn this cross-sectional study, 1,978 adolescents (1,017 girls) aged 13.0–18.5 years from the AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes) study were included. Particular dietary habits (breakfast, mid-morning snack, lunch, afternoon snack, dinner, and nighttime snack, as well as time spent eating, number of meals, consumption of soft drinks, and ready-to-eat foods) and LTPA were self-reported and analyzed as dichotomic variables (yes/no). The sum of six skinfold thicknesses and waist circumference (WC) values were the main body fatness variables.ResultSkinfolds and WC values were lower in adolescents who reported consumption of mid-morning snack, afternoon snack, more than four meals per day, and an adequate speed of eating, independently of participation in LTPA. Moreover, a beneficial influence of breakfast consumption on skinfolds and WC values was observed in those adolescent boys who did not participate in LTPA (p for interactions = .044 and .040, respectively).ConclusionsIn Spanish adolescents, certain healthy dietary habits (i.e., mid-morning snack, afternoon snack, > 4 meals per day, adequate eating speed) are associated with lower body fatness, independently of engaging in LTPA. In addition, among boys with non-LTPA, those who skipped breakfast showed the highest body fatness values, indicating a beneficial influence of daily breakfast on body fat in this particular group.     

Potentiation of therapeutic immune responses against malignancies with monoclonal antibodies.

Immunotherapeutic monoclonal antibodies (mAbs) can be defined as those that exert their functions by tampering with immune system cell molecules, causing an enhancement of antitumor immune responses. Some of these antibodies are agonistic ligands for surface receptors involved in the activation of lymphocytes and/or antigen-presenting cells, whereas others are antagonists of mechanisms that normally limit the intensity of immune reactions. Several mAbs of this category have been described to display in vivo antitumor activity in mouse models. Only anti-CTLA-4 (CD152) mAb has entered clinical trials, but the preclinical effects described for anti-CD40, anti-CD137 (4-1BB), anti-CD102 (intercellular adhesion molecule-2), and regulatory T cell-depleting mAbs should lead to their prompt clinical development. Their use in combination with immunizations against tumor antigens has been reported to be endowed with synergistic properties. This new group of antitumor agents holds promise for at least additive effects with conventional therapies of cancer and deserves intensive translational research.     

Effects of hydroxytyrosol-enriched sunflower oil consumption on CVD risk factors

Inclusion of biophenols in traditional foods transforms them into functional foods that may help to decrease CVD risk. The aim of the present study was to determine whether the consumption of hydroxytyrosol-enriched sunflower oil (HSO) improves certain CVD biomarker values. A total of twenty-two healthy volunteers participated in a cross-over study involving two 3-week periods, separated by a 2-week washout period, in which volunteers consumed 800-1275 μg/d [corrected] of either HSO (45-50 mg/d of hydroxytyrosol) or non-enriched (control) sunflower oil. Total cholesterol, LDL-cholesterol, HDL-cholesterol, arylesterase activity, oxidised LDL and soluble vascular cell adhesion molecule (sVCAM-1) levels were measured in the plasma obtained at the beginning and at the end of each treatment period. The HSO group displayed a significantly higher level (P < 0·01) of arylesterase activity and significantly lower levels of oxidised LDL and sVCAM-1 (both P < 0·05) than the control group. These results suggest that HSO may help prevent CVD.     

Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.     

Physical activity as a preventive measure against overweight, obesity, infections, allergies and cardiovascular disease risk factors in adolescents: AFINOS Study protocol

Background  

Prior studies addressing the impacts of regular physical activity or sedentary habits on the immune system have been conducted in adults and laboratory settings. Thus, it is practically unknown how a healthy active lifestyle could affect low-grade inflammation processes, infections or allergies in young persons. The AFINOS Study was designed to determine the relationship between the regular physical activity levels of adolescents and overweight, infection, and allergies along with the presence of metabolic and immunological biomarkers of a deteriorated health status. A further objective of the AFINOS Study is to assess the health status and lifestyle habits of an adolescent population in an effort to identify any protective factors that could be used as preventive measures, since many chronic diseases and their associated co-morbidities often persist from adolescence into adulthood.     

Surface proteins of C6/36 cells involved in dengue virus 4 binding and entry

Dengue virus (DENV) is the causative agent of the most important mosquito-borne viral disease, which is endemic to over 100 countries in tropical and subtropical areas of the world. It is transmitted to humans by Aedes mosquitoes. The first step in the viral infection of host cells is virion attachment to the plasma membrane, which is mediated by specific surface molecules. There are several molecules that participate in DENV infection of mosquitoes, but only a few have been identified. In this work, we co-purified 4 proteins from C6/36 cells using a recombinant DENV 4 E protein and identified them as 70 kDa Heat Shock and 70 kDa Heat Shock cognate proteins (HSP70/HSc70), Binding immunoglobulin protein (BiP), Thioredoxin/protein disulphide isomerase (PDI), and 44 kDa Endoplasmic reticulum resident protein (ERp44) via matrix-assisted laser desorption/ionisation time of flight (Maldi-ToF) analysis. Using immunofluorescence and flow cytometry assays, we observed re-localisation of HSP70/HSc70 and, to a lesser extent, BiP to the plasma membrane under stress conditions, such as during DENV infection. By performing binding and infection assays independently, we found that all 4 proteins participate in both processes, but to differing extents: HSP70/HSc70 is the most critical component, while ERp44 is less important. Viral infection was not inhibited when the cells were incubated with antibodies against all of the surface proteins after virus binding, which suggests that DENV entry to C6/36 cells is mediated by these proteins at the same step and not sequentially.     

Moderate alcohol consumption and the immune system: a review

Increasing evidence suggests that light to moderate amounts of polyphenol-rich alcoholic beverages like wine or beer could have health benefits. Scientists have long debated the effects of alcohol on immune function, showing on the one hand, that high doses of alcohol consumption can directly suppress a wide range of immune responses, and that alcohol abuse is associated with an increased incidence of a number of infectious diseases. On the other hand, moderate alcohol consumption seems to have a beneficial impact on the immune system compared to alcohol abuse or abstinence. Therefore, the link between alcohol consumption, immune response, as well as infectious and inflammatory processes remains not completely understood. With this in mind, it is important to realise that other factors, unrelated or indirectly related to immune function, like drinking patterns, beverage type, amount of alcohol, or gender differences, will affect the influence that alcohol consumption may have on the immune system. This review summarises published data describing the effects that light to moderate amounts of polyphenol-rich beverages like wine or beer seem to have on immunity in healthy adults.