Smoking, fat mass and activation of the tumor necrosis factor-α pathway

Fernández-Real, José Manuel; Broch, Montserrat; Vendrell, Joan; Ricart, Wifredo

doi:10.1038/sj.ijo.0802472

Cited by 41 publications

(37 citation statements)

References 31 publications

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“…(26,27) Fernandez-Real et al reported that, in a mixed lymphocyte reaction, leptin supported T cell differentiation toward the Th1 phenotype. (28) In the present study, IFN-γ levels were positively correlated with the asthma symptom scores and negatively correlated with FEV 1 % only in obese children. Our data suggest that, in the presence of high leptin levels, there is an increase in IFN-γ production by Th1-polarized cells, (22,28) with aggravation of airway inflammation and clinical outcomes that are more severe.…”

Section: Resultsmentioning

confidence: 55%

“…(28) In the present study, IFN-γ levels were positively correlated with the asthma symptom scores and negatively correlated with FEV 1 % only in obese children. Our data suggest that, in the presence of high leptin levels, there is an increase in IFN-γ production by Th1-polarized cells, (22,28) with aggravation of airway inflammation and clinical outcomes that are more severe. Our data are corroborated by Rastogi et al, who demonstrated that obese children with asthma had lower FEV 1 /FVC ratios than did non-obese children with asthma and children without asthma, and that the FEV 1 /FVC ratio was negatively correlated with serum IFN-γ levels.…”

Section: Resultsmentioning

confidence: 55%

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The influence of leptin on Th1/Th2 balance in obese children with asthma

et al. 2013

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Objective: In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. Methods: We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. Results: Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV 1 (% of predicted) than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group. Conclusions: Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity.Keywords: Leptin; Asthma; Interferon-gamma; Interleukin-4. ResumoObjetivo: A obesidade induz a produção de leptina em asmáticos e está associada à gravidade da doença. Nosso objetivo foi avaliar os níveis de leptina sérica e seu efeito no equilíbrio Th1/Th2 em crianças asmáticas obesas e não obesas e investigar a associação desses níveis com desfechos clínicos. Métodos: O estudo envolveu 50 crianças atópicas com diagnóstico médico de asma persistente moderada a grave e 20 controles. Os asmáticos foram agrupados como obesos (n = 25) e não obesos (n = 25) de acordo com o percentil do índice de massa corpórea. Amostras de sangue periférico foram coletadas de todos os sujeitos, e os níveis de leptina, IFN-γ e IL-4 foram determinados. A gravidade da asma foi avaliada por um escore de sintomas de asma, e os resultados foram correlacionados com os parâmetros estudados. Resultados: Os níveis séricos de leptina foram significativamente maiores nos asmáticos obesos do que nos asmáticos não obesos, assim como nos asmáticos comparados aos controles, enquanto os níveis de IFN-γ foram significativamente maiores e os de IL-4 foram significativamente menores nos asmáticos obesos do que nos asmáticos não obesos. Os asmáticos obesos tiveram maiores escores de sintomas de asma e VEF 1 (% do previsto) si...

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Section: Resultsmentioning

confidence: 55%

Section: Resultsmentioning

confidence: 55%

The influence of leptin on Th1/Th2 balance in obese children with asthma

et al. 2013

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“…Similar results were reported by Fernandez-Real and coworkers. 22 In conclusion, we found that heavy smoking could induce a significant increase in serum TNF-a and CRP levels, suggesting the imbalance between the proinflammatory and antiinflammatory factors. The concentration of TNF-a was elevated in the serum of healthy heavy smokers in a dose dependent manner.…”

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confidence: 88%

“…Zoppini and coworkers 21 reported that type 1 diabetic smokers had increased serum levels of the p55 receptor compared to healthy nonsmokers or diabetic nonsmokers. Another study conducted by Fernandez-Real et al 22 showed that circulating levels of p75 receptors were significantly higher in healthy smokers than in nonsmokers, despite the lower fat mass in the smoker group. Both soluble TNF-a receptors (sTNFRs), p55 and p75, are increased in the serum of patients with different inflammatory diseases.…”

Section: Petrescu Et Almentioning

confidence: 99%

Tumor necrosis factor-α serum levels in healthy smokers and nonsmokers

Voican¹

2010

COPD

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Background: Tobacco smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD) development. Inhaled cigarette smoke can induce tumor necrosis factor-a (TNF-a) production by alveolar macrophages, which in turn may enhance the production of metalloproteinases (MMPs). MMPs have been involved in mediating airway inflammation and lung destruction. Objectives: We aimed to measure the TNF-a serum levels in healthy heavy smokers and healthy nonsmokers to determine the dose-response relationship based on the cigarette smoke exposure. Subjects and methods:We included in our study 43 healthy heavy smokers and 19 healthy nonsmokers (the control group). The smokers group was classified as less than one pack, one pack, and more than one pack per day. A clinical and paraclinical evaluation was performed in both groups, without any evidence of infection or COPD. The serum levels of TNF-a were assessed by ELISA. Results: The TNF-a serum levels were significantly higher for the group of smokers compared to the group of nonsmokers (P , 0.004). We also noticed an increased TNF-a concentration in the serum of smokers with more than one pack per day compared with those with less than one pack per day (P , 0.03). There was a positive correlation between the serum level of TNF-a and tobacco smoke exposure. Conclusions:The high levels of TNF-a in the serum of smokers suggest an imbalance between the proinflammatory and anti-inflammatory factors as a result of tobacco smoke exposure. The concentration of TNF-a is elevated in the serum of healthy heavy smokers in a cigarette dosedependent manner. We speculate that the serum level of TNF-a might be a useful biomarker for the selection of heavy smokers with a high risk of developing smoke induced pulmonary diseases.

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“…30 However, this is in contrast to FernandezReal and colleagues, who found increased concentrations of soluble TNFR2 in obese smokers, and identified both fat mass and smoking as independent contributors to 4% of the variance of soluble TNFR2. 31 It is also possible that the prolonged storage (eight years at −80°) for TNFR2 may have played a role. We hypothesize that there is a delicate balance between pro-and antiinflammatory cytokines and receptors which we were unable to resolve in our sample.…”

Section: Individual Markersmentioning

confidence: 99%

Relation of smoking status to a panel of inflammatory markers: The Framingham offspring

et al. 2008

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Aims-We sought to investigate the hypothesis that smoking is accompanied by systemic inflammation.Methods and Results-We examined the relation of smoking to 11 systemic inflammatory markers in Framingham Study participants (n=2944, mean age 60 years, 55% women, 12% ethnic minorities) examined from 1998-2001. The cohort was divided into never (n=1149), former (n=1424), and current smokers with last cigarette >6 hours (n=134) or ≤6 hours (n=237) prior to phlebotomy. In multivariable-adjusted models there were significant overall between-smoking group differences (defined as p<0.0045 to account for multiple testing) for every inflammatory marker tested, except for serum CD40 ligand (CD40L), myeloperoxidase (MPO) and tumor necrosis factor receptor-2 (TNFR2). With multivariable-adjustment, pair-wise comparisons with never smokers revealed that former smokers had significantly lower concentrations of plasma CD40L (p<0.0001) and higher concentrations of C-reactive protein (p=0.002).Conclusions-As opposed to never smokers, those with acute cigarette smoke exposure (≤6 hours) had significantly higher concentrations of all markers (p<0.0001) except serum CD40L, MPO, and TNFR2; plasma CD40L were significantly lower. Compared with never smokers, cigarette smokers have significantly elevated concentrations of most circulating inflammatory markers, consistent with the hypothesis that smoking is associated with a systemic inflammatory state.

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Smoking, fat mass and activation of the tumor necrosis factor-α pathway

Cited by 41 publications

References 31 publications

The influence of leptin on Th1/Th2 balance in obese children with asthma

The influence of leptin on Th1/Th2 balance in obese children with asthma

Tumor necrosis factor-α serum levels in healthy smokers and nonsmokers

Relation of smoking status to a panel of inflammatory markers: The Framingham offspring

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Smoking, fat mass and activation of the tumor necrosis factor-α pathway

Cited by 41 publications

References 31 publications

The influence of leptin on Th1/Th2 balance in obese children with asthma

The influence of leptin on Th1/Th2 balance in obese children with asthma

Tumor necrosis factor-&alpha; serum levels in healthy smokers and nonsmokers

Relation of smoking status to a panel of inflammatory markers: The Framingham offspring

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Tumor necrosis factor-α serum levels in healthy smokers and nonsmokers